Interobserver variability of patient positioning using four different CT datasets for image registration in lung stereotactic body radiotherapy.

PURPOSE: To assess the impact of different reference CT datasets on manual image registration with free-breathing three-dimensional (3D) cone beam CTs (FB-CBCT) for patient positioning by several observers. METHODS: For 48 patients with lung lesions, manual image registration with FB-CBCTs was performed by four observers. A slow planning CT (PCT), average intensity projection (AIP), maximum intensity projection (MIP), and midventilation CT (MidV) were used as reference images. Couch shift differences between the four reference CT datasets for each observer as well as shift differences between the observers for the same reference CT dataset were determined. Statistical analyses were performed and correlations between the registration differences and the 3D tumor motion and the CBCT score were calculated. RESULTS: The mean 3D shift difference between different reference CT datasets was the smallest for AIPvsMIP (range 1.1-2.2 mm) and the largest for MidVvsPCT (2.8-3.5 mm) with differences >10 mm. The 3D shifts showed partially significant correlations to 3D tumor motion and CBCT score. The interobserver comparison for the same reference CTs resulted in the smallest ∆3D mean differences and mean ∆3D standard deviation for ∆AIP (1.5 ± 0.7 mm, 0.7 ± 0.4 mm). The maximal 3D shift difference between observers was 10.4 mm (∆MidV). Both 3D tumor motion and mean CBCT score correlated with the shift differences (Rs = 0.336-0.740). CONCLUSION: The applied reference CT dataset impacts image registration and causes interobserver variabilities. The 3D tumor motion and CBCT quality affect shift differences. The smallest differences were found for AIP which might be the most appropriate CT dataset for image registration with FB-CBCT.

Registration uncertainties between 3D cone beam computed tomography and different reference CT datasets in lung stereotactic body radiation therapy.

BACKGROUND: The aim of this study was to analyze differences in couch shifts (setup errors) resulting from image registration of different CT datasets with free breathing cone beam CTs (FB-CBCT). As well automatic as manual image registrations were performed and registration results were correlated to tumor characteristics. METHODS: FB-CBCT image registration was performed for 49 patients with lung lesions using slow planning CT (PCT), average intensity projection (AIP), maximum intensity projection (MIP) and mid-ventilation CTs (MidV) as reference images. Both, automatic and manual image registrations were applied. Shift differences were evaluated between the registered CT datasets for automatic and manual registration, respectively. Furthermore, differences between automatic and manual registration were analyzed for the same CT datasets. The registration results were statistically analyzed and correlated to tumor characteristics (3D tumor motion, tumor volume, superior-inferior (SI) distance, tumor environment). RESULTS: Median 3D shift differences over all patients were between 0.5 mm (AIPvsMIP) and 1.9 mm (MIPvsPCT and MidVvsPCT) for the automatic registration and between 1.8 mm (AIPvsPCT) and 2.8 mm (MIPvsPCT and MidVvsPCT) for the manual registration. For some patients, large shift differences (>5.0 mm) were found (maximum 10.5 mm, automatic registration). Comparing automatic vs manual registrations for the same reference CTs, ∆AIP achieved the smallest (1.1 mm) and ∆MIP the largest (1.9 mm) median 3D shift differences. The standard deviation (variability) for the 3D shift differences was also the smallest for ∆AIP (1.1 mm). Significant correlations (p < 0.01) between 3D shift difference and 3D tumor motion (AIPvsMIP, MIPvsMidV) and SI distance (AIPvsMIP) (automatic) and also for 3D tumor motion (∆PCT, ∆MidV; automatic vs manual) were found. CONCLUSIONS: Using different CT datasets for image registration with FB-CBCTs can result in different 3D couch shifts. Manual registrations achieved partly different 3D shifts than automatic registrations. AIP CTs yielded the smallest shift differences and might be the most appropriate CT dataset for registration with 3D FB-CBCTs.

Hsp70--a biomarker for tumor detection and monitoring of outcome of radiation therapy in patients with squamous cell carcinoma of the head and neck.

BACKGROUND: Tumor but not normal cells frequently overexpress heat shock protein 70 (Hsp70) and present it on their cell surface (mHsp70) from where it can be actively released. Therefore, membrane (mHsp70) and soluble Hsp70 (sHsp70) were investigated as potential tumor biomarkers and for monitoring the outcome of radiation therapy. METHODS: Biopsies and blood were collected from patients with squamous cell carcinoma of the head and neck (SCCHN) at different time points (before, during therapy and in the follow-up period). Hsp70 membrane expression was determined on single cell suspensions of tumor biopsies and reference tissues by flow cytometry, sHsp70 protein and antibody levels were determined in the serum of patients and healthy donors by ELISA and NK cell markers that are related to the presence of sHsp70 were analyzed in the patient's peripheral blood lymphocytes (PBL). RESULTS: Tumor biopsies exhibited significantly increased mHsp70 expression levels compared to the reference tissue. Soluble Hsp70 levels were significantly higher in SCCHN patients compared to healthy human volunteers and high mHsp70 expression levels on tumor cells were associated with high sHsp70 levels in the serum of patients. Following surgery and radiotherapy sHsp70 levels in patients dropped in patients without tumor relapse in the follow-up period. In contrast to sHsp70 protein, anti-Hsp70 antibody levels remained nearly unaltered in the serum of SCCHN patients before and after therapy. Furthermore, sHsp70 protein but not anti-Hsp70 antibody levels were found to be associated with the tumor volume in SCCHN patients before start of therapy. The expression densities of the activatory NK cell markers CD56, CD94, NKG2D, NKp30, Nkp44, and NKp46 differed in patients following therapeutic intervention. A significant increase in the density of NKG2D was observed in SCCHN patients in the follow-up period after surgery and radiotherapy. CONCLUSION: We suggest sHsp70 as a potential biomarker for detecting tumors and for monitoring the clinical outcome of radiotherapy in SCCHN patients.