Abstract
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Objectives: Lung cancer is one of the most prevalent cancers worldwide, and non-small cell lung cancer (NSCLC) accounts for about 85-90% of all lung tumor types. Carbon ion radiation therapy (CIRT) has achieved outcomes comparable to surgery due to its excellent dose-concentration and high biological effectiveness. However, two-year progression-free survival of patients treated with CIRT for locally advanced lung cancer is reported as 40%. C11-methionine (MET) is an amino acid radiotracer known to show tumor-specific accumulation and MET-PET/CT imaging is useful in evaluating lung tumors. However, the correlation between MET-PET/CT imaging biomarkers and prognosis in NSCLC patients is still unknown. The aim of this study was to investigate the predictive values of MET-PET/CT in patients treated with CIRT for NSCLC.
Methods: Sixty consecutive patients (36 males and 24 females; mean age 73.3y; range 51-89y) with locally advanced NSCLC who underwent MET-PET/CT prior to CIRT between 2007 and 2012 were enrolled. Patients were treated with 40-50 Gy of CIRT. The mean follow-up period was 77.3 months. For quantitative analysis of PET image data, metabolic tumor volume was obtained with a threshold of standardized sptake value (SUV) greater than 1.5. Tumor contouring on MET-PET/CT image was determined by a consensus of two board-certified diagnostic radiologists. Univariate and Multivariate Cox proportional hazard regression analyses and Kaplan-Meir analyses were performed to assess the predictive value for disease-free survival (DFS) among a diameter of solid tumor component (Solid-Diameter), SUVmax, Metabolic Tumor Volume (MTV), Total Lesion Metabolism of the amino acid (TLM), and clinical factors. Statistical analyses were calculated with SPSS statistical software, version 26 with P values of less than 0.05 considered statistically significant.
Results: The mean SUVmax of the tumor was 3.53±1.0. Univariate Cox proportional hazard regression analyses showed that SUVmax (p<0.05, HR 3.22 95% CI 1.21-8.56), MTV (p<0.005, HR 4.45, 95% CI 1.78-11.2), and TLM (p<0.005, HR 0.249, 95% CI 0.10-0.62) were significant prognostic factors for DFS. While, the Solid-Diameter, age, sex, and the treatment radiation dose were not significant prognostic factors for DFS. After checking multicollinearity, multivariate Cox hazard analysis was performed with five elements: Solid-Diameter, SUVmax, MTV, age, and sex. MTV was revealed to be the only independent prognostic factor (p<0.05, HR 0.257, 95% CI 0.072-0.923). Kaplan-Meier analysis of MTV demonstrated that patients with MTV lower than 6ml had longer DFS (p<0.001).
Conclusions: Metabolic Tumor Volume (thresholds of SUV 1.5) in MET-PET/CT would be a useful predictor of disease-free survival of NSCLC treated with CIRT.
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