Image-based lung functional radiotherapy planning for non-small cell lung cancer.

BACKGROUND: This simulation study assessed the feasibility and impact of incorporating additional information from lung perfusion single-photon emission computed tomography (SPECT) into intensity-modulated radiotherapy planning for the treatment of non-small cell lung cancer (NSCLC). METHODS: In this simulation study, data of 13 patients with stage I-III NSCLC previously treated by radio(chemo)therapy were used. The SPECT was fused together with radiotherapy planning CT. Functional lung regions (FL) and non-functional lung regions (nFL) were defined based on SPECT images. Four treatment plans were created for each patient: an IMRT and a VMAT plan with planning CT (anatomical plans), and an IMRT and a VMATplan which integrate the additional information from lung perfusion scintigraphy (function plans). Dosimetric parameters were compared between all plans for PTV parameters and normal tissue preservation, focusing on optimizing the lung volume receiving at least 20 Gy (V20Gy). RESULTS: Compared to anatomical plans, functional IMRT and functional VMAT plans reduced functional lung V20Gy in all cases of local and diffuse hypoperfusion patterns of SPECT defects. Similar results were observed for functional lung V30Gy and median dose to functional lung Dmean, but were not statistically significant in any group. A significant increase in non-functional lung V20Gy resulted in both functional plans. There were no significant differences in conformity or heterogeneity indices or PTV median doses between either pair of anatomical and functional plans. CONCLUSION: The incorporation of functional imaging for radiotherapy planning in non-small cell lung cancer is feasible and appears to be beneficial in preserving a functional lung in non-small cell lung cancer.

Tumor lesion glycolysis and tumor lesion proliferation for response prediction and prognostic differentiation in patients with advanced non-small cell lung cancer treated with erlotinib.

PURPOSE: The aim was to assess the value of tumor lesion glycolysis (TLG) and tumor lesion proliferation (TLP) determined by FDG and 3'-deoxy-3'-F-fluorothymidine (FLT) PET for response prediction and prognostic differentiation in patients with advanced non-small cell lung cancer (NSCLC) treated with erlotinib. PATIENTS AND METHODS: FDG-PET and FLT-PET were performed in 30 patients with untreated Stage IV NSCLC before start of therapy, 1 (early) and 6 (late) weeks after erlotinib treatment. Functional tumor volume parameters including TLG in FDG-PET and TLP in FLT-PET were measured in the sum of up to 5 lesions per scan. Metabolic response was assessed using different cutoff values for percentage changes of TLG and TLP. Absolute baseline and residual levels of TLG and TLP were used for dichotomizing the patients into 2 groups. Kaplan-Meier analysis and the log-rank test were performed to analyze the association with progression-free survival (PFS). RESULTS: Patients with a metabolic response measured by early changes of TLP and late changes of TLG and TLP showed a significantly better PFS than metabolically nonresponding patients. A lower cutoff value of 20% or 30% for definition of metabolic response showed better differentiation between metabolically responding and nonresponding patients in cases where the 45% cutoff value revealed no significant results. Furthermore, patients with lower absolute early and late residual TLG and TLP levels had a significantly prolonged PFS. In contrast, absolute baseline TLG and TLP levels showed no significant association with PFS. CONCLUSIONS: In patients with advanced NSCLC, percentage changes of TLG and TLP and absolute residual TLG and TLP levels under erlotinib treatment emerged as strong predictive factors for PFS. Our findings indicate that a cutoff value of 20% or 30% for definition of metabolic response measured by percentage changes of TLG and TLP provides suitable results for response prediction, which should be further validated.

Predictive value of early and late residual 18F-fluorodeoxyglucose and 18F-fluorothymidine uptake using different SUV measurements in patients with non-small-cell lung cancer treated with erlotinib.

PURPOSE: To evaluate the predictive value of early and late residual (18)F-fluorodeoxyglucose (FDG) and (18)F-fluorothymidine (FLT) uptake using different SUV measurements in PET in patients with advanced non-small-cell lung cancer (NSCLC) treated with erlotinib. METHODS: We retrospectively reviewed data from 30 patients with untreated stage IV NSCLC who had undergone a combined FDG PET and FLT PET scan at 1 week (early) and 6 weeks (late) after the start of erlotinib treatment. Early and late residual FDG and FLT uptake were measured in up to five lesions per scan with different quantitative standardized uptake values (SUV(max), SUV(2Dpeak), SUV(3Dpeak), SUV(50), SUV(A50), SUV(A41)) and compared with short-term outcome (progression vs. nonprogression after 6 weeks of erlotinib treatment). Receiver-operating characteristics (ROC) curve analysis was used to determine the optimal cut-off value for detecting nonprogression after 6 weeks. Kaplan-Meier analysis and the log-rank test were used to evaluate the association between residual uptake and progression-free survival (PFS). RESULTS: Nonprogression after 6 weeks was associated with a significantly lower early and late residual FDG uptake, measured with different quantitative parameters. In contrast, nonprogression after 6 weeks was not associated with early and late residual FLT uptake. Furthermore, patients with a lower early residual FDG uptake measured in terms of SUV(max) and SUV(2Dpeak) had a significantly prolonged PFS (282 days vs. 118 days; p = 0.022) than patients with higher values. Similarly, lower late residual FDG uptake and early residual FLT uptake measured in terms of SUV(3Dpeak), SUV(A50) and SUV(A41), and late FLT uptake measured in terms of SUV(3Dpeak) and SUV(A50) was associated with an improved PFS. CONCLUSION: Early and late residual FDG uptake, measured using different quantitative SUV parameters, are predictive factors for short-term outcome in patients with advanced NSCLC treated with erlotinib. Additionally, low residual FDG and FLT uptake early and late in the course of erlotinib treatment is associated with improved PFS.

Quantitative analysis of response to treatment with erlotinib in advanced non-small cell lung cancer using 18F-FDG and 3'-deoxy-3'-18F-fluorothymidine PET.

UNLABELLED: The purpose of this study was to evaluate the relevance for the prediction of clinical benefit of first-line treatment with erlotinib using different quantitative parameters for PET with both (18)F-FDG and 3'-deoxy-3'-(18)F-fluorothymidine ((18)F-FLT) in patients with advanced non-small cell lung cancer. METHODS: Data were used from a prospective trial involving patients with untreated stage IV non-small cell lung cancer. (18)F-FDG PET and (18)F-FLT PET were performed before and 1 (early) and 6 (late) weeks after erlotinib treatment. Several quantitative standardized uptake values (SUVs) using different definitions of volumes of interest with varying isocontours (maximum SUV [SUV(max)], 2-dimensional peak SUV [SUV(2Dpeak)], 3-dimensional [3D] peak SUV [SUV(3Dpeak)], 3D isocontour at 50% of the maximum pixel value [SUV(50)], 3D isocontour at 50% adapted for background [SUV(A50)], 3D isocontour at 41% of the maximum pixel value adapted for background [SUV(A41)], 3D isocontour at 70% of the maximum pixel value [SUV(70)], 3D isocontour at 70% adapted for background [SUV(A70)], and relative SUV threshold level [SUV(RTL)]) and metabolically active volume measurements were obtained in the hottest single tumor lesion and in the sum of up to 5 lesions per scan in 30 patients. Metabolic response was defined as a minimum reduction of 30% in each of the different SUVs and as a minimum reduction of 45% in metabolically active volume. Progression-free survival (PFS) was compared between patients with and without metabolic response measured with each of the different parameters, using Kaplan-Meier statistics and a log-rank test. RESULTS: Patients with a metabolic response on early (18)F-FDG PET and (18)F-FLT PET in the hottest single tumor lesion as well as in the sum of up to 5 lesions per scan had a significantly longer PFS, regardless of the method used to calculate SUV. However, the highest significance was obtained for SUV(max), SUV(50), SUV(A50), and SUV(A41.) Patients with a metabolic response measured by SUV(max) and SUV(3Dpeak) on late (18)F-FDG PET in the hottest single tumor lesion had a significantly longer PFS. Furthermore, Kaplan-Meier analyses showed a strong association between PFS and response seen by metabolically active volume, measured either in early (18)F-FLT or in late (18)F-FDG. CONCLUSION: Early (18)F-FDG PET and (18)F-FLT PET can predict PFS regardless of the method used for SUV calculation. However, SUV(max), SUV(50), SUV(A50), and SUV(A41) measured with (18)F-FDG might be the best robust SUV to use for early response prediction. Metabolically active volume measurement in early (18)F-FLT PET and late (18)F-FDG PET may have an additional predictive value in monitoring response in patients with advanced non-small cell lung cancer treated with erlotinib.

Delayed gadolinium-enhanced MRI of cartilage (dGEMRIC) and morphologic MRI of cartilage in the long-term follow-up after Legg-Calvé-Perthes disease (LCPD).

INTRODUCTION: The purpose of the present study was to evaluate the feasibility of delayed gadolinium-enhanced magnetic resonance imaging of cartilage (dGEMRIC) in the detection of cartilage changes versus morphologic imaging in the long-term course of Legg-Calvé-Perthes disease (LCPD). METHODS: A total of 31 hips in 26 patients (mean age, 30.0years; range, 18-54years) who were diagnosed with LCPD in childhood were included. Twenty-one radiographically normal contralateral hips served as controls. dGEMRIC indices of femoral and acetabular cartilage in the weight-bearing zone. Cartilage morphology was classified on radial PD-weighted images according to the modified Outerbridge classification. RESULTS: Mean dGEMRIC values of cartilage were significantly lower in hips after LCPD than in the radiographically normal contralateral hips (513±100 ms vs. 579±103 ms; P=0.026). In 24 out of 31 LCPD hips and in 4 out of 21 radiographically normal contralateral hips, morphological cartilage changes were noted. Analysis of variance analysis revealed a significant influence of Outerbridge grading on decreased T1-values (P=0.031). CONCLUSION: Our results suggest that dGEMRIC at 1.5 T is suitable to assess cartilage quality changes in the long-term follow-up after LCPD. The evaluation of biochemical cartilage quality with dGEMRIC may provide additional information about early cartilage changes occurring without visible alterations of cartilage morphology.

Assessment of early cartilage degeneration after slipped capital femoral epiphysis using T2 and T2* mapping.

BACKGROUND: T2 and T2* mapping are novel tools to assess cartilage quality. PURPOSE: To evaluate hip cartilage quality in the long-term follow-up of patients with slipped capital femoral epiphysis (SCFE) with T2 and T2* mapping. MATERIAL AND METHODS: Thirty-three patients (19 men, 14 women, mean age 24 ± 6.0 years, range 18-51 years) with a history of SCFE in 41 hips and 10 healthy controls (seven men, mean age 22 ± 4 years) were included. Follow-up period was 12 ± 6 (range 4-39 years) years. Coronal T2 and T2* mapping were performed on a 1.5 T scanner. T2 and T2* values of the hip articular cartilage were determined in the medial, central, and lateral portion of the hip within the weight bearing zone. Clinical symptoms including pain were assessed with the Harris hip score. Statistical analysis was performed using Mann-Whitney U test and Spearman rank sum test. RESULTS: In hips after SCFE T2 (central portion: 25.71 ms ± 4.84 ms vs. 29.71 ms ± 7.04 ms, p<0.05) and T2* (central portion: 20.76 ms ± 3.17 ms vs. 23.06 ms ± 2.68 ms, P<0.01) of cartilage were significantly lower, compared to controls. The differences were most apparent in the lateral portion of the hip articular cartilage. Abnormal cartilage T2 and T2* were not associated with hip pain or impaired hip function. SCFE was unilateral in 23 cases (70%). In the patients' unaffected hips without SCFE, areas of significantly reduced T2 (central portion: 26.07 ms ± 4.27 ms, P<0.05) and T2* (lateral portion: 23.23 ms ± 2.45 vs. 25.11 ms ± 3.01 ms, P<0.05) were noted. CONCLUSION: T2 and T2* mapping of the hip in patients after SCFE are significantly different from healthy controls and may offer additional information about cartilage quality.

Delayed gadolinium-enhanced magnetic resonance imaging of cartilage (dGEMRIC), after slipped capital femoral epiphysis.

OBJECTIVE: The aim of this study was to assess the glycosaminoglycan (GAG) content in hip joint cartilage in mature hips with a history of slipped capital femoral epiphysis (SCFE) using delayed gadolinium-enhanced MRI of cartilage (dGEMRIC). METHODS: 28 young-adult subjects (32 hips) with a mean age of 23.8 ± 4.0 years (range: 18.1-30.5 years) who were treated for mild or moderate SCFE in adolescence were included into the study. Hip function and clinical symptoms were evaluated with the Harris hip score (HHS) system at the time of MRI. Plain radiographic evaluation included Tonnis grading, measurement of the minimal joint space width (JSW) and alpha-angle measurement. The alpha-angle values were used to classify three sub-groups: group 1=subjects with normal femoral head-neck offset (alpha-angle <50°), group 2=subjects with mild offset decrease (alpha-angle 50°-60°), and group 3=subjects with severe offset decrease (alpha-angle >60°). RESULTS: There was statistically significant difference noted for the T1(Gd) values, lateral and central, between group 1 and group 3 (p-values=0.038 and 0.041). The T1(Gd) values measured within the lateral portion were slightly lower compared with the T1(Gd) values measured within the central portion that was at a statistically significance level (p-value <0.001). HHS, Tonnis grades and JSW revealed no statistically significant difference. CONCLUSION: By using dGEMRIC in the mid-term follow-up of SCFE we were able to reveal degenerative changes even in the absence of joint space narrowing that seem to be related to the degree of offset pathology. The dGEMRIC technique may be a potential diagnostic modality in the follow-up evaluation of SCFE.

Delayed gadolinium-enhanced magnetic resonance imaging of cartilage in the long-term follow-up after Perthes disease.

BACKGROUND: Aim of this study was to assess the glycosaminoglycan content in hip joint cartilage in mature hips with a history of Legg-Calvé-Perthes (LCPD) disease using delayed gadolinium-enhanced magnetic resonance imaging of cartilage (dGEMRIC). METHODS: Thirty one hips in 27 adults (mean age: 30.5+/-10.9 y) with LCPD in childhood were included. Mean follow-up after diagnosis was 24.5+/-11.4 years. Clinical symptoms and standard radiographic parameters were evaluated. dGEMRIC indices were calculated as T1(Gd) mean values in four coronal MRI slices medially, centrally, and laterally. For comparison, the morphologically normal appearing contra-lateral hips (21 hips) were assessed. RESULTS: The following T1(Gd) values for the LCPD group were noted: medial (507+/-100 ms), central (543+/-104 ms), and lateral (553+/-105 ms). The total T1(Gd) mean value was 534+/-104 ms. The difference between LCPD and normal hips was statistically significant only for the medial compartment (P=0.018). CONCLUSIONS: Hip joint cartilage after LCPD shows a significant glycosaminoglycan loss in the medial compartment while this decrease is less apparent centrally and laterally. dGEMRIC allows direct assessment of cartilage matrix biochemistry and may depict the complex damage pattern of hip joint cartilage after LCPD spatially and qualitatively better than other radiographic methods. LEVEL OF EVIDENCE: Prognostic study, Level II-1 (retrospective study).

MRI morphometry, cartilage damage and impaired function in the follow-up after slipped capital femoral epiphysis.

OBJECTIVE: To assess rotation deficits, asphericity of the femoral head and localisation of cartilage damage in the follow-up after slipped capital femoral epiphysis (SCFE). MATERIALS AND METHODS: Magnetic resonance imaging studies were obtained in adult patients with a history of SCFE. A total of 35 hips after SCFE in 26 patients (mean age 24.1 +/- 6.5, mean follow-up 11.9 +/- 6.1 years) were evaluated. The control group comprised 20 healthy hips from 10 young adults with an average age of 23.9 +/- 3.7 years. The MR protocol included a T1-weighted sequence with a 3D volumetric interpolated breath-hold sequence and a radial 2D proton density-weighted sequence around the femoral neck. Images were evaluated for alpha angle and cartilage damage in five positions around the femoral head. Hip function was evaluated at the time of MRI and correlated with MRI results. Mann-Whitney U test and Spearman's correlation coefficient were used for statistical analysis. RESULTS: In the hips after SCFE alpha angles were significantly increased in the anterosuperior (74.1 degrees +/- 18.8 degrees ) and superior (72.5 degrees +/- 21.5 degrees ) positions and decreased in the posterior position (25.0 degrees +/- 7.2 degrees ). Cartilage damage was dominant in the anterosuperior and superior positions. Impaired rotation significantly correlated with increased anterosuperior, superior and posterosuperior alpha angles. CONCLUSION: The data support an anterosuperior and superior cam-type deformity of the femoral head-neck junction in the follow-up after SCFE. MRI after SCFE can be used to assess anterosuperior and superior alpha angles, since the anterior alpha angle by itself may underestimate asphericity and is not associated with rotation deficits.

Voxel-based analyses of magnetization transfer imaging of the brain in hepatic encephalopathy.

AIM: To evaluate the spatial distribution of cerebral abnormalities in cirrhotic subjects with and without hepatic encephalopathy (HE) found with magnetization transfer imaging (MTI). METHODS: Nineteen cirrhotic patients graded from neurologically normal to HE grade 2 and 18 healthy control subjects underwent magnetic resonance imaging. They gave institutional-review-board-approved written consent. Magnetization transfer ratio (MTR) maps were generated from MTI. We tested for significant differences compared to the control group using statistical non-parametric mapping (SnPM) for a voxel-based evaluation. RESULTS: The MTR of grey and white matter was lower in subjects with more severe HE. Changes were found in patients with cirrhosis without neurological deficits in the basal ganglia and bilateral white matter. The loss in magnetization transfer increased in severity and spatial extent in patients with overt HE. Patients with HE grade 2 showed an MTR decrease in white and grey matter: the maximum loss of magnetization transfer effect was located in the basal ganglia [SnPM (pseudo-)t = 17.98, P = 0.0001]. CONCLUSION: The distribution of MTR changes in HE points to an early involvement of basal ganglia and white matter in HE.