Abstract
Objectives: (1.1) to evaluate the association between baseline 18F-FDG PET/CT semi-quantitative parameters of the primary lesion with progression free survival (PFS), overall survival (OS) and response to immunotherapy, in advanced non-small cell lung carcinoma (NSCLC) patients eligible for immunotherapy; (1.2) to evaluate the application of radiomics analysis of the primary lesion to identify features predictive of response to immunotherapy; (1.3) to evaluate if tumor burden assessed by 18F-FDG PET/CT (N and M factors) is associated with PFS and OS. Materials and Methods: we retrospectively analyzed clinical records of advanced NCSLC patients (stage IIIb/c or stage IV) candidate to immunotherapy who performed 18F-FDG PET/CT before treatment to stage the disease. Fifty-seven (57) patients were included in the analysis (F:M 17:40; median age = 69 years old). Notably, 38/57 of patients had adenocarcinoma (AC), 10/57 squamous cell carcinoma (SCC) and 9/57 were not otherwise specified (NOS). Overall, 47.4% patients were stage IVA, 42.1% IVB and 8.8% IIIB. Immunotherapy was performed as front-line therapy in 42/57 patients and as second line therapy after chemotherapy platinum-based in 15/57. The median follow up after starting immunotherapy was 10 months (range: 1.5–68.6). Therapy response was assessed by RECIST 1.1 criteria (CT evaluation every 4 cycles of therapy) in 48/57 patients or when not feasible by clinical and laboratory data (fast disease progression or worsening of patient clinical condition in nine patients). Radiomics analysis was performed by applying regions of interest (ROIs) of the primary tumor delineated manually by two operators and semi-automatically applying a threshold at 40% of SUVmax. Results: (1.1) metabolic tumor volume (MTV) (p = 0.028) and total lesion glycolysis (TLG) (p = 0.035) were significantly associated with progressive vs. non-progressive disease status. Patients with higher values of MTV and TLG had higher probability of disease progression, compared to those patients presenting with lower values. SUVmax did not show correlation with PD status, PFS and OS. MTV (p = 0.027) and TLG (p = 0.022) also resulted in being significantly different among PR, SD and PD groups, while SUVmax was confirmed to not be associated with response to therapy (p = 0.427). (1.2) We observed the association of several radiomics features with PD status. Namely, patients with high tumor volume, TLG and heterogeneity expressed by “skewness” and “kurtosis” had a higher probability of failing immunotherapy. (1.3) M status at 18F-FDG PET/CT was significantly associated with PFS (p = 0.002) and OS (p = 0.049). No significant associations were observed for N status. Conclusions: 18F-FDG PET/CT performed before the start of immunotherapy might be an important prognostic tool able to predict the disease progression and response to immunotherapy in patients with advanced NSCLC, since MTV, TLG and radiomics features (volume and heterogeneity) are associated with disease progression.
Highlights
Lung cancer remains the leading cause of cancer-related death, despite continuous progresses in diagnosis and therapy [1]
Different immune checkpoint inhibitors have been approved in the second line setting on the basis of an improving in overall survival (OS) compared to chemotherapy, irrespective to PDL1 expression or with a programmed death ligand-1 (PD-L1) expression ≥1% for pembrolizumab
The objectives of this study were: (1.1) to evaluate the association between 18F-FDG PET/CT baseline semi-quantitative parameters of the primary lesion in advanced Non-small cell lung carcinoma (NSCLC) patients eligible for immunotherapy with patient’s outcome (PFS and OS) and response to immunotherapy, (1.2) to evaluate the application of radiomics analysis of the primary lesion for texture analysis to extract characteristics from PET/CT images to represent tumor pathology or heterogeneity, (1.3) to evaluate if tumor burden assessed by 18F-FDG PET/CT, as nodal (N) and metastatic (M)
Summary
Lung cancer remains the leading cause of cancer-related death, despite continuous progresses in diagnosis and therapy [1]. Non-small cell lung carcinoma (NSCLC) accounts for 80–85% of all cases of lung cancer [1]. In almost half of the patients, the diagnosis of NSCLC is performed when the disease is already in advanced stages (stage III or stage IV), having an estimated overall 5-year survival rate of 18% [2]. In more than half of patients, the diagnosis of NSCLC is performed when the disease is already in advanced stage with an estimated overall 5-year survival rate of 18% [2,3]. Different immune checkpoint inhibitors have been approved in the second line setting on the basis of an improving in overall survival (OS) compared to chemotherapy, irrespective to PDL1 expression or with a PD-L1 expression ≥1% for pembrolizumab
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