We investigated whether the combination of primary tumor and nodal 18F-FDG PET parameters predict survival outcomes in patients with nodal metastatic non-small cell lung cancer (NSCLC) without distant metastasis. We retrospectively extracted pre-treatment 18F-FDG PET parameters from 89 nodal-positive NSCLC patients (stage IIB–IIIC). The Cox proportional hazard model was used to identify independent prognosticators of overall survival (OS) and progression-free survival (PFS). We devised survival stratification models based on the independent prognosticators and compared the model to the American Joint Committee on Cancer (AJCC) staging system using Harrell’s concordance index (c-index). Our results demonstrated that total TLG (the combination of primary tumor and nodal total lesion glycolysis) and age were independent risk factors for unfavorable OS (p < 0.001 and p = 0.001) and PFS (both p < 0.001), while the Eastern Cooperative Oncology Group scale independently predicted poor OS (p = 0.022). Our models based on the independent prognosticators outperformed the AJCC staging system (c-index = 0.732 versus 0.544 for OS and c-index = 0.672 versus 0.521 for PFS, both p < 0.001). Our results indicate that incorporating total TLG with clinical factors may refine risk stratification in nodal metastatic NSCLC patients and may facilitate tailored therapeutic strategies in this patient group.
Background
To investigate the survival prognostic value of the radiomic features of 18F-FDG PET in patients who had EGFR (epidermal growth factor receptor) mutated lung adenocarcinoma and received targeted TKI (tyrosine kinase inhibitor) treatment.
Methods
Fifty-one patients with stage III-IV lung adenocarcinoma and actionable EGFR mutation who received first-line TKI were retrospectively analyzed. All patients underwent pretreatment 18F-FDG PET/CT, and we calculated the PET-derived radiomic features. Cox proportional hazard model was used to examine the association between the radiomic features and the survival outcomes, including progression-free survival (PFS) and overall survival (OS). A score model was established according to the independent prognostic predictors and we compared this model to the TNM staging system using Harrell's concordance index (c-index).
Results
Forty-eight patients (94.1%) experienced disease progression and 41 patients (80.4%) died. Primary tumor SUV entropy > 5.36, and presence of pleural effusion were independently associated with worse OS (both p < 0.001) and PFS (p = 0.001, and 0.003, respectively). We used these two survival predictors to devise a scoring system (score 0–2). Patients with a score of 1 or 2 had a worse survival than those with a score of 0 (HR for OS: 3.6, p = 0.006 for score 1, and HR: 21.8, p < 0.001 for score 2; HR for PFS: 2.2, p = 0.027 for score 1 and HR: 8.8, p < 0.001 for score 2). Our scoring system surpassed the TNM staging system (c-index = 0.691 versus 0.574, p = 0.013 for OS, and c-index = 0.649 versus 0.517, p = 0.004 for PFS).
Conclusions
In this preliminary study, combining PET radiomics with clinical risk factors may improve survival stratification in stage III-IV lung adenocarcinoma with actionable EFGR mutation. Our proposed scoring system may assist with optimization of individualized treatment strategies in these patients.
Radiogenomic heterogeneity features in 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET) have become popular in non-small cell lung cancer (NSCLC) research. However, the reliabilities of genomic heterogeneity features and of PET-based glycolytic features in different image matrix sizes have yet to be thoroughly tested. We conducted a prospective study with 46 NSCLC patients to assess the intra-class correlation coefficient (ICC) of different genomic heterogeneity features. We also tested the ICC of PET-based heterogeneity features from different image matrix sizes. The association of radiogenomic features with clinical data was also examined. The entropy-based genomic heterogeneity feature (ICC = 0.736) is more reliable than the median-based feature (ICC = −0.416). The PET-based glycolytic entropy was insensitive to image matrix size change (ICC = 0.958) and remained reliable in tumors with a metabolic volume of <10 mL (ICC = 0.894). The glycolytic entropy is also significantly associated with advanced cancer stages (p = 0.011). We conclude that the entropy-based radiogenomic features are reliable and may serve as ideal biomarkers for research and further clinical use for NSCLC.
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