Nodal Staging, Natural Growth And Metabolic Response To Treatment Evaluated With Serial¹⁸F-fluorodeoxyglucose Positron Emission Tomography/Computed Tomography Scans In Radical Radiotherapy Candidates With Non-small Cell Lung Cancer

Purpose:Nodal staging of non-small-cell lung cancer (NSCLC) is crucial in evaluation of prognosis and determination of therapeutic strategy. This study aimed to determine the negative predictive value (NPV) of combined positron emission tomography and computed tomography (PET-CT) in patients with stage I (T1-2N0) NSCLC and to investigate the possible risk factors for occult nodal disease.Methods:Studies investigating the performance of PET in conjunction with CT in the nodal staging of stage I NSCLC were identified in the MEDLINE database. The initiative of standards for reporting of diagnostic accuracy (STARD) was used to ensure study quality. Pathologic assessments through mediastinoscopy or thoracotomy were required as the reference standard for evaluation of PET-CT accuracy. Stata-based meta-analysis was applied to calculate the individual and pooled NPVs.Results:Ten studies with a total of1122patients with stage Ⅰ(T1-2N0) NSCLC were eligible for analysis. The NPVs of combined PET and CT for mediastinal metastases were0.94in T1disease and0.89in T2disease. Including both T1disease and T2disease, the NPVs were0.93for mediastinal metastases and0.87for overall nodal metastases. Adenocarcinoma histology type (risk ratio [RR],2.72) and high fluorine-18(18F) fluorodeoxyglucose (FDG) uptake in the primary lesion were associated with greater risk of occult nodal metastases.Conclusions:Although overall occult nodal metastases in clinical stage T1-2N0NSCLC is not infrequent, combined PET and CT provide a favorable NPV for mediastinal metastases in T1N0NSCLC, suggesting a low yield from routine invasive staging procedures for this subgroup of patients. Purpose:The aims of this study were to:1) estimate the volumetric and metabolic growth rate of non-small cell lung cancer (NSCLC),2) evaluate disease progression prior to treatment, and3) explore the effects of tumor growth rate and time to treatment (TTT) on survival outcome.Methods:Patients with inoperable Stage Ⅰ-Ⅲ NSCLC with serial pre-treatment PET/CT scans were eligible for this study. PET-derived metabolic tumor volumes (PET-MTV) and CT-derived gross tumor volumes (CT-GTV) were contoured using PET/CT information. Normalized standardized uptake values (NSUV) in tumors including the NSUVmean and NSUVmax were measured. Tumor growth rates expressed as doubling time (DT) were estimated using an exponential model. Pre-treatment disease progression was defined as the development of any new site of disease on PET/CT and change in TNM Stage (AJCC7th Ed.) was recorded. Patient-outcome data was analyzed with respect to overall and progression free survival.Results:Thirty-four patients with a median inter-scan interval (ISI) of43days and TTT of48days were analyzed. Tumor volumes showed remarkable inter-scan growth while NSUV did not increase significantly. The DT for PET-MTV, CT-GTV, NSUVmean and NSUVmax were124,139,597, and333days, respectively. Pre-treatment disease progression occurred in20.6%patients with longer ISI being a significant risk factor (OR=1.027,p=0.02). The optimal threshold ISI to predict progression was58days (4.8%vs.46.2%, p=0.007). Neither tumor growth rates nor TTT were significantly correlated to overall survival or progression free survival.Conclusions:NSCLC displays rapid tumor volume growth whereas tumor metabolic activity is relatively stable over the same time period. Longer delays before initiation of treatment are associated with higher risk of pre-treatment disease progression. Purpose:Based on18F FDG PET-CT in patients with NSCLC, this study aimed to:1) compare multiple methods in quantifying post-treatment FDG uptake reduction in NSCLC;2) compare qualitative and semi-quantitative assessment of categorical metabolic response;3) evaluate the prognostic value of categorical metabolic response and4) investigate the relationship between numerical post-treatment change of metabolic activity and overall survival (OS) and explore an optimal cutoff to distinguish better responders.Methods:This is a secondary analysis of a series of prospective studies. Enrolled patients with NSCLC underwent18F-fluorodeoxyglucose PET/CT imaging within2weeks prior to, midway through, and following radiation treatment (RT). Metabolic therapeutic response was assessed using following methods;1) visual assessment,2) semi-quantitative assessment based on FDG uptake reduction using three types of calculation including absolute maximum SUV (ASUV), mediastinum blood pool (MBP) normalized maximum SUV (NSUV-A) and liver normalized maximum SUV (NSUV-L). Kappa coefficient was used to evaluate the agreement between various categorical variables and survival analyses were adopted to analyze the effect of multiple response criteria on overall survival (OS).Results:Forty-four patients (36M:8F, median age70±10) were eligible for present analysis. The interval between end of RT and post-RT PET/CT scan ranged from45to176days, with a median of93days. Mean SUV of liver was significantly higher than that of MBP at all time points of studies (P<0.001). Neither MBP nor liver had significant metabolic change over time. Reduction percentage of ASUV, NSUV-A and NSUV-L were highly correlated with each other, resulting in the during-and post-treatment intraclass coefficients of0.919and0.943, respectively. There was a moderate agreement between ASUV and NSUV derived response distribution (Kappa coefficient=0.535) and a dramatic concordance between categorical response determined by NSUV-A and NSUV-L (Kappa coefficient=1.0), whereas a poor agreement was observed between visual and semi-quantitative responses (Kappa coefficient=0.393). Categorical responses were significantly correlated with OS independent of employed response assessment criteria (P<0.001) and those with complete metabolic response (CMR) obtained the longest OS. As continuous variable, reduction percentage of NSUV-A showed pronounced association with OS (hazard ratio, HR=0.213). Seventy percent of NSUV-A reduction was identified as another optimal cutoff to distinguish patients with most significant difference in OS (P<0.001)Conclusions:For NSCLC patients acquiring radical chemoradiaotherapy, semi-quantitative metabolic therapeutic response distributions using different interpretation criteria show good correlation between each other, whereas have great discrepancy with that based on visual assessment, most often in the CMR identification. Current categorical responses demonstrate significant association with overall survival and the combination of visual and semi-quantitative assessment can further improve the predictability of long-term survival. As continuous variable, more numerical reduction percentage is correlated with prolonged overall survival. Seventy percent of metabolic reduction may be another optimal threshold to distinguish responders from non-responders.