Prognostic value of metabolic activity of the psoas muscle evaluated by preoperative ¹⁸F-FDG PET-CT in breast cancer: a retrospective cross-sectional study

This was a retrospective cross-sectional study that reviewed 375 women with breast cancer who underwent breast-conserving surgical resection for the treatment of invasive breast cancer (invasive ductal carcinoma [IDC]) between January 2014 and December 2014. Participants with pathologies other than IDC, carcinoma in situ, initially metastatic breast cancer, and double primary malignancies were excluded. Patients with thyroid cancer, stage I uterine cancer, and skin malignancies other than malignant melanoma that had been completely resected were included. Finally, 288 patients were enrolled. All patients regularly visited the hospital for follow-up after completion of therapy according to the protocol, which was developed based on results from physical examinations and additional diagnostic imaging studies, including chest/abdomen computed tomography, bone scan, and torso ¹⁸F-FDG PET-CT. The recurrence of disease was defined as confirmation of local recurrence or distant metastasis.

This retrospective study was approved by the Institutional Review Board (IRB) of the university hospital, which waived the requirement for written consent (IRB 2011–032-097). The study was performed in accordance with the relevant guidelines and regulations.

All patients were evaluated with ¹⁸F-FDG PET-CT for preoperative staging. After fasting for at least 6 h, patients were injected with 5.2 MBq of ¹⁸F-FDG per kilogram of body weight. Serum glucose levels were less than 120 mg/dL before ¹⁸F-FDG administration. The ¹⁸F-FDG PET-CT imaging studies were performed 60 min after the intravenous injection of ¹⁸F-FDG. The PET-CT scanner used was Biograph 40 (Siemens, Knoxville, TN, USA). The emission scan time per bed position was 3 min, and six bed positions were acquired. The PET data were obtained using a high-resolution whole-body scanner with an axial field of view of 21.6 cm. The average axial resolution varied between 2.0 mm full width at half maximum in the center and 2.4 mm at 28 cm. The average total PET-CT examination time was 20 min. Attenuation correction was performed for all patients with iterative reconstruction. The PET-CT images were analyzed in three different planes: transverse, coronal, and sagittal.

To obtain a maximum value and an average standardized uptake value (SUV) of the psoas muscle and the liver, the region of interest (ROI) was placed as follows: The 1.00 cm²sized circular ROI was drawn manually on the axial image of the ¹⁸F-FDG PET-CT. Bilateral psoas muscle activity was measured using the CT image acquired during ¹⁸F-FDG PET-CT and circular ROI at the L2 lumbar vertebra. The average SUVs of the bilateral psoas muscle were normalized using the mean SUV of the liver to exclude potential factors affect SUV [15]. The ratio of ROI activity to the activity of the reference region significantly improved the detection of regional changes in metabolism by intra-subject comparison (SUVR). To measure the mean SUV of the liver, an elliptical ROI was placed on the right lobe of the liver, in the middle part, to avoid a mismatch between the CT and PET images and to avoid artifacts due to respiratory motion, and the values were averaged. SUVRmax was calculated as the ratio of the maximum SUV of the bilateral psoas muscle to the mean SUV of the liver. SUVRmean was calculated as the ratio of the mean SUV of the bilateral psoas muscle to the mean SUV of the liver (Formula 1 &2).

Continuous data are expressed as the median and interquartile range (IQR), and categorical data are presented as the frequency and percentage. For the K-M survival analysis which need binary data, we should find out cutoff value from the continuous variables of SUVRmax and SUVRmean. For the optimal cutoff levels for SUVRmax and SUVRmean for the patients who were survived as disease free or not, a receiver operating characteristic (ROC) analysis was based on the evaluation of the area under the curve (AUC) and 95% confidence interval. The empirical ROC is a plot of the true positive rate versus the false positive rate for all possible cut-off values. In those cut-off values, we could choose one threshold value which has the best performance for the discrimination of the patients who had progressive disease or not. Disease-free survival (DFS) was estimated using the Kaplan–Meier method, and statistical differences were assessed using the log-rank test. A multivariate analysis was performed using the Cox proportional hazards model including variables that had P-values < 0.05 in the univariate analyses. The statistical analyses were performed using the Statistical Package for the Social Sciences Statistics for Windows version 22.0 (IBM Corp., Armonk, NY, USA). A P-value less than 0.05 was considered as significant.

Table 1 shows the baseline characteristics of the 288 enrolled patients with breast cancer. The median follow-up period was 72.5 (IQR, 0.684–0.842) months for all eligible patients. The median age at the time of surgery was 52 (IQR, 44.986–59.629) years. The median value for body mass index (BMI) was 22.803 (IQR, 20.812–25.333) kg/m². Less than 10% of the patients had diabetes mellitus and dyslipidemia. A Chi-squared test or Fisher’s exact test revealed that age, level of BMI, prevalence of diabetes mellitus, rate of menopause, prevalence of dyslipidemia, level of Ki-67, rate of chemotherapy, and rate of radiotherapy were not different between the recurrence and no recurrence groups. Higher T and N stages, ER and PR negativity, HER2 positivity, triple-negative breast cancer (TNBC), mastectomy, high SUVRmean, and high SUVRmax were significantly observed in the recurrence group (Table 1).

Based on the ROC curve, the optimal cutoff value for SUVRmax to predict DFS was 0.565, with an AUC of 0.519 (sensitivity 31.6%, specificity 91.3%). The optimal cutoff value for SUVRmean to predict DFS was 0.464, with an AUC of 0.504 (sensitivity 42.1%, specificity 73.9%). Patients were divided into two groups, stratified by the optimal cutoff value of the SUVRmax: 262 patients (90.972%) were assigned to the low SUVRmax group, and 26 patients (9.028%) were assigned to the high SUVRmax group. Using the cutoff value of the SUVRmean, 206 patients (71.528%) were assigned to the low SUVRmean group, and 82 patients (28.472%) were assigned to the high SUVRmean group.

The univariate analyses identified a higher T stage, higher N stage, ER negativity, PR negativity, HER2 positivity, TNBC, mastectomy (rather than breast-conserving surgery), SUVRmean > 0.464, and SUVRmax > 0.565 as significant factors that predicted disease recurrence after initial disease management (Table 2). The final multivariate Cox regression analysis showed that N3 stage (hazard ratio [HR] = 5.347, P = 0.031) was an independent factor for recurrence (Table 2). The DFS curves according to N stages are shown in Fig. 1. Moreover, increased SUVRmax (HR = 4.987, P = 0.050) showed strong potential as an independent prognostic factor for cancer recurrence. Figure 2 shows division of the DFS curves based on the level of SUVRmax.