Predictive and prognostic role of functional imaging of head and neck squamous cell carcinomas.
ABSTRACT Predicting radiotherapy (RT) treatment response and eventual locoregional disease control is an important component of the ongoing effort to improve the therapeutic ratio in the management of head and neck squamous cell carcinomas. The development of clinically useful predictive and prognostic imaging biomarkers has been limited by significant tumor heterogeneity in both the tumor and its microenvironment. Various advanced imaging techniques have been evaluated in the head and neck squamous cell carcinoma patient, which now offer a strategy to identify and quantify this heterogeneity, characterizing the tumor at baseline and its response to RT. The most promising of these techniques include dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI), DCE computed tomography, diffusion-weighted MRI, and (18)F-fluoromisonidazole positron emission tomography (PET) all relying on the spatiotemporal quantification of a contrast agent within a region of interest that can be further analyzed by various pharmacokinetic models. Despite the small study populations, several consistent observations have been reported that warrant further validation. Features associated with a favorable RT response include tumors with an effective vasculature characterized by rapid and high influx rates of the contrast agent and its effective clearance with little or no regions of hypoxia. (18)F-deoxyglucose-PET imaging remains an active area of investigation with the metabolic tumor volume parameter appearing to offer potential predictive value. Characterizing changes during a course of RT may offer greater predictive value. Both DCE-MRI and diffusion-weighted MRI can identify physiological changes within the first 1-2 weeks of treatment that are correlated with long-term clinical outcome. Identifying persistent hypoxia with (18)F-fluoromisonidazole-PET during a course of RT suggests an increased risk of relapse. Whether this is due to an inability to favorably remodel the tumor's vasculature has not been clearly demonstrated to date. Future research goals include the need to further validate these promising imaging biomarkers especially in larger cohorts of patients, characterizing the optimal threshold cutoffs and to refine the predictive value by incorporating the assessments of early tumor responses to therapy that offer the potential for increased specificity because it reflects the biological stress responses.
- SourceAvailable from: Chien-Jang Wu[show abstract] [hide abstract]
ABSTRACT: To investigate the correlation between diffusion-weighted (DW) and dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) derived parameters and radioresponsiveness of Lewis lung carcinoma (LLC) tumor. LLC tumor growth in C57BL/6 mouse limb was used for the experiment. The tumors were irradiated with 10 Gy×5, or 30 Gy×2 vs. sham irradiation. Fourteen tumors were subjected to DW-MRI and DCE-MRI pre-radiotherapy and weekly imaging after radiotherapy. The temporal changes in apparent diffusion coefficient (ADC) and DCE-MRI derived parameters (K(trans), kep, ve, and vp) were correlated with tumor size, and were histologically compared with CD31 staining of resected tumors. The 10 Gy×5 dose inhibited tumor growth for a week, while 30 Gy×2 controlled tumor growth for a 3-week observation period. One week after radiotherapy (week 2), irradiated tumors showed significantly higher values of ADC than untreated ones (10 Gy×5, p = 0.004; 30 Gy×2, p = 0.01). Significantly higher values of ve were shown earlier by 30 Gy×2 vs. sham (p = 0.01) and 10 Gy×5 vs. sham irradiation (p = 0.05). Sustained higher ve from 10 Gy×5 compared to sham irradiated tumors was evident at week 3 (p = 0.016) and week 4 (p = 0.046). A 13.8% early increase in ADC for 30 Gy×2 tumor group (p = 0.002) and a 16.5% increase for 10 Gy×5 group were noted (p = 0.01) vs. sham irradiation (which showed a 2.2% decrease). No differences were found for K(trans), kep, or vp. Both radiotherapy groups demonstrated significant reduction in microvessel counts. Early increase in ADC and ve correlated with tumor control by irradiation.PLoS ONE 01/2013; 8(5):e62762. · 3.73 Impact Factor