Prognostic Value of Combing Primary Tumor and Nodal Glycolytic-Volumetric Parameters of 18F-FDG PET in Patients with Non-Small Cell Lung Cancer and Regional Lymph Node Metastasis

Abstract

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.

Keywords: 18F-FDG; PET; glycolytic; non-small cell lung cancer; prognosis; volumetric.

Figure 1

The method used for feature extraction from ¹⁸F-FDG PET. VOI, volume-of-interest; SUV, standardized uptake value; TLG, total lesion glycolysis; NTSUVR, nodal to primary tumor SUV_max ratio; NTTLGR, nodal to primary tumor TLG ratio; TNSUVproduct, product of primary tumor and nodal SUV_max.

Figure 2

The Kaplan–Meier curves for OS and PFS in patients with nodal metastatic NSCLC without distant metastasis. Survival was stratified according to the eighth edition of the AJCC system (a,b) and our survival prediction model (c,d). OS, overall survival; PFS, progression-free survival; AJCC, American Joint Committee on Cancer.

Figure 3

The Kaplan–Meier curves depicting OS and PFS stratified by our prediction model in subgroups of different initial treatments. The use of our model in subgroups that underwent curative surgery or neoadjuvant CCRT followed by surgery (a,b) and in initial non-surgical subgroup (c,d). OS, overall survival; PFS, progression-free survival; CCRT, concurrent chemoradiotherapy.

Figure 4

Survival stratification according to the independent risk factors in our study. The ¹⁸F-FDG PET/CT images for a 50-year-old woman with adenocarcinoma in the left upper lobe and subaortic nodal metastasis, indicated by arrows in the panels (a–c). The clinical staging was cT2aN2M0, stage IIIA. The total TLG was 14.9 and the ECOG status was 0. The patient had no poor survival risk factor (hazards were both 1 for an unfavorable OS and poor PFS) and she underwent lobectomy of the left upper lobe and mediastinal lymph node dissection. The pathological staging was pT2aN2M0, stage IIIA. She underwent adjuvant chemotherapy and is now alive without recurrence (d). The OS and PFS were 116 and 115 months, respectively. A 75-year-old man with adenocarcinoma in the right lower lobe and ipsilateral hilar nodal metastasis, indicated by arrows in the panels (e–g). The clinical staging was cT2bN1M0, stage IIB. The total TLG was 246.6 (>81) and the ECOG status was 1 (the hazards for unfavorable OS and poor PFS were 16.8 and 3.3, respectively). The patient received definitive CCRT (2 Gy/fraction daily to a targeted dose of 66 Gy) and marked tumor shrinkage was observed (h). However, the patient experienced progression of the primary tumor 15.9 months after definitive CCRT, indicated by the arrow in the panel (i). The patient eventually died of lung cancer progression, with an OS of 24.0 months and PFS of 15.9 months. TLG, total lesion glycolysis; OS, overall survival; PFS, progression-free survival; CCRT, concurrent chemoradiotherapy.