The Prognostic Value Of 18F-Fluorodeoxyglucose Positron Emission Tomography-Computed Tomography In Non-Small Cell Lung Cancer

Part Ⅰ. Primary tumor SUVmax on 18F-FDG PET/CT:correlation with clinicopathologic prognostic factors in non-small cell lung cancerObjective:To assess the relationship between preoperative maximum standardized uptake value (SUVmax) on 18F-FDG PET/CT and clinicopathologic parameters in patients with surgically treated non-small cell lung cancer (NSCLC).Methods:From October 2006 to January 2013, a total of 540 patients (348 men and 192 women; age range 27-84 years, median age 60 years) with histologically confirmed non-small cell lung cancer, who had undergone both preoperative 18F-FDG PET/CT and curative surgery in our institution, were analyzed retrospectively in this study. Any patients who received preoperative adjuvant or neoadjuvant therapy were excluded. Primary tumor 18F-FDG uptake, measured as SUVmax corrected for lean body mass, was compared among different clinicopathologic parameters and correlated with age, tumor size, histologic grade and pathologic TNM stage. Histologic classification was made according to the 2004 edition of the World Health Organization (WHO) histological classification of lung tumors,344 tumors were adenocarcinomas (AC, non-BAC type), 146 tumors were squamous cell carcinomas (SCC),28 tumors were bronchioloalveolar carcinomas (BAC),10 tumors were adenosquamous carcinomas (ASC), and 12 tumors were other types (OT, including 6 large cell carcinomas,5 sarcomatoid carcinomas and 1 lymphoepitheloid carcinoma). Histologic differentiation was graded according to conventional histologic criteria, where grade Ⅰ (n=76) represents highly, grade Ⅱ (n=251) moderately, and grade Ⅲ (n=213) poorly differentiated or undifferentiated. Pathologic TNM stage was assigned according to the seventh edition of the Cancer Staging Manual of the American Joint Committee on Cancer (AJCC),281 cases were stage Ⅰ,104 cases were stage Ⅱ,127 cases were stage Ⅲ, and 28 cases were stage Ⅳ. Statistical analyses were performed using SPSS statistical software (version 19.0).Results:The SUVmax was 6.4±4.4m (range 0.3-28.1) for all subjects. The SUVmax was significantly differenced between men and women (7.6±4.6 vs.4.3±3.1),≥60 years group and <60 years group (6.8±4.3 vs.6.0±4.6), smoker and non-smoker (7.9 ±4.6 vs.4.7±3.5), central type and peripheral type (9.1±4.3 vs.5.5±4.1),≥3 cm group and< 3 cm group (8.4±4.5 vs. 4.2±3.1), and between elevated tumor markers (TMs) level and normal TMs level (7.5±4.5 vs. 4.9±3.9) (all P<0.05). The SUVmax in ascending order was BAC (1.3±1.1), AC (5.1±3.4), ASC (8.5±2.8), SCC (9.9±4.6) and OT (10.9±5.1) based on histologic type, and significant difference was identified among BAC, AC and SCC (all P=0.000), and between BAC and ASC (P=0.000), BAC and OT (P=0.000), AC and ASC (P< 0.01), AC and OT (P=0.000). The SUVmax in ascending order was grade I (2.4±2.2), grade Ⅱ (5.9±3.9) and grade Ⅲ (8.4±4.4) based on histologic grade, and significant difference was identified among grade Ⅰ, grade Ⅱ and grade Ⅲ (all P=0.000). Significant differences were also found in the SUVmax between stage Ⅰ (4.6±.61) and stage Ⅱ (8.6±.6), stage Ⅲ (8.4±.43) and stage Ⅳ (7.4±.4) (all P< 0.01), however, no significant differences were found among stage Ⅱ, stage Ⅲ and stage Ⅳ (all P> 0.05). The SUVmax was positively correlated with tumor size (r= 0.564, P=0.000), histologic grade (r=0.492, P=0.000), T stage (r=0.306, P=0.000), N stage (r=0.368, P=0.000), and TNM stage (r=0.437, P=0.000).Conclusion:There were significant differences in the SUVmax of primary tumor by gender, age, smoking history, tumor location, tumor size, serum tumor markers level, histologic type, histologic grade and pathologic stage. There were significant positive correlations between SUVmax and tumor size, histologic grade and pathologic stage. Our findings may suggest that SUVmax is potentially a very important prognostic factor for NSCLC patients.Part II. Prognostic significance of SUVmax on 18F-FDG PET/CT in patients with surgically resected non-small cell lung cancerObjective:Non-small cell lung cancer (NSCLC) is a major medical problem worldwide with high disease specific mortality rate and poor prognosis. Although many clinical, pathologic, routine laboratory markers, molecular biologic markers, and gene signatures have been suggested as possible univariate or independent prognostic factors for NSCLC, very few validated prognostic factors are available in clinical practice. To date, TNM stage is still the strongest prognostic factor for NSCLC, however, additional parameters are required for explaining variability of survival. The present study focused on the role of maximum standardized uptake value (SUVmax) on 18F-FDG PET/CT in predicting the outcome in patients with surgically treated NSCLC.Methods:One hundred sixty-seven NSCLC patients (110 men and 57 women, mean age 60.4 years, age range 27-84 years) were enrolled in this study. All patients underwent preoperative F-FDG PET/CT scan followed by curative surgery. Any patients who received preoperative adjuvant or neoadjuvant therapy were excluded. FDG uptake in the primary tumor was measured by SUVmax (corrected for lean body mass). Patient’s survival time was defined as the time interval from the date of operation to the date of death or last follow-up. The SUVmax, gender, age, smoking history, tumor location, tumor size, tumor markers level, histologic type, differentiation grade and pTNM stage were analyzed for association with overall survival (OS), using the log-rank test for univariate survival analysis and the Cox proportional hazards model for multivariate analysis. A P value less than 0.05 was considered to be statistically significant.Results:The median SUVmax was 5.4 (range 0.7-20.4) for all subjects. The median follow-up was 43 months (range 3.5-81 months). At the time of last follow-up,49 patients had died due to disease recurrence or metastasis. The overall 1-,2- and 3-year survival rates for the entire cohort were 94%,83% and 76%, respectively. On univariate analysis of overall survival (OS), the SUVmax, gender, age, smoking status, tumor location, primary tumor size, tumor markers level, histologic type, differentiation grade and pTNM stage were all significantly associated with outcome (all P<0.05), and the patients with lower SUVmax (< 5.4) showed significantly higher OS compared with higher SUVmax (≥5.4) (Log-rank P=0.000; HR 5.35,95%CI 2.67-10.74). On multivariate analysis, the SUVmax, pTNM stage, tumor size and age were all independent predictors for OS (all P< 0.05), and the patients with SUVmax ≥5.4 had a higher mortality risk than those with SUVmax< 5.4 (multivariable adjusted HR 2.76, 95% CI 1.24-6.11).Conclusion:The primary tumor SUVmax on 18F-FDG PET/CT has an independently significant prognostic value for overall survival in patients with surgically treated non-small cell lung cancer. It could be used to identify a high-risk population in non-small cell lung cancer patients with the same pathologic stage, who would benefit most from adjuvant or individualized therapies.