18F-FDG Pet Parameters and Radiomics Features Analysis in Advanced Nsclc Treated with Immunotherapy as Predictors of Therapy Response and Survival

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.

[18F]FDG PET immunotherapy radiomics signature (iRADIOMICS) predicts response of non-small-cell lung cancer patients treated with pembrolizumab

“…Polverari et al . observed significant differences in tumour heterogeneity (as defined by kurtosis and skewness) between patients with progressive disease (PD) and non-PD 21 , while the study by Mu et al . proposed a combined PET and CT radiomics signature for predicting patient PFS and OS.…”

“…On the other hand, few immunotherapy clinical studies examined possible non-invasive imaging biomarkers, but there is still a lack of research performed in NSCLC patients. 14 Three retrospective anti-PD-1 studies showed associations of pre-treatment sum of maximum standardized uptake values (SUV max ) of all lesions (SUV maxwb ) 19 , SUV max of the most avid lesion 20 , and volumetric parameters (metabolic tumour volume [MTV], and total lesion glycolysis [TLG]) 21 , with NSCLC patient response as defined by RECIST. However, significant correlations of these features with OS were not observed.…”

Utility of [18F] Fluoro-Deoxyglucose Positron Emission Tomography/Computed Tomography for Staging and Therapy Response Evaluation in Pediatric Rhabdomyosarcoma: A Case Series and Literature Review

“…In advanced non-smallcell lung carcinoma, patients with higher values of MTV and TLG had higher probability of disease progression compared to those patients presenting with lower values, while SUV max did not show a correlation with progressive disease (PD) status. MTV also resulted in being significantly different among partial response (PR), stable disease (SD), and PD groups, while SUV max was confirmed to not be associated with response to therapy (25). Besides, some papers have correlated metabolic parameters derived from the baseline PET to metabolic therapy response.…”

What Is the Role of Imaging in Cancers?

“…Table 1 shows a summary of the topics and the papers included for each topic [ 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 ]. The majority of papers are focused on prostate cancer (PCa) and radiomics.…”

“…Indeed, radiomics can be used as a tool for the prediction of outcomes in terms of response to therapy or prognosis in patients undergoing immune check point inhibitors, as stated by Polverari et al [ 29 ]. The use of imaging as a predictive biomarker of response to immunotherapy has been discussed by some authors [ 5 , 6 , 7 ], in the present issue.…”