Intra- and inter-observer variability in dependence of T1-time correction for common dynamic contrast enhanced MRI parameters in prostate cancer patients.

BACKGROUND: Dynamic contrast enhanced (DCE) MRI parameters are potential biomarkers to characterise tumour vasculature and distinguish it from the non-cancerous blood vessel system within the prostate. However, the inevitable presence of intra- and inter-observer variabilities is challenging in this context. Additionally, pre-contrast T1-time correction is a prerequisite to gain quantitative DCE parameters in the first place. The current study investigated the effect of individualized T1-time correction on intra- and inter-reader variability for quantitative DCE-parameters in prostatic lesions. METHODS: In this IRB-approved retrospective study, two experienced radiologists assessed DCE parameters using individually measured (A) and fixed (B) T1-times twice with a time difference of three weeks. The dataset consisted of 35 MRI-guided biopsy-proven prostate cancer lesions. Limits of agreement (LoA) and coefficients of variability (CoV) were calculated to assess intra- and inter-reader variabilities of the parameters. RESULTS: With exception of kep, for all DCE parameters both intra- and inter-reader CoV were smaller in B compared to A. Absolute kep values were largely insensitive to T1-time correction induced bias. The mean intra-reader CoVs [5%, 95% percentile] (over all four DCE parameters and both readers) were 6.7% [0.5%, 15.1%] in A and 3.9% [0.2%, 11.0%] in B. The inter-reader CoVs were 9.0% [0.6%, 25.8%] (A) and 7.0% [0.3%, 25.4%] (B). CONCLUSIONS: T1-time correction has a significant influence on the intra- and inter-reader variability. By applying individually measured T1-time correction, both intra- and inter-observer variability were found to increase. Out of all investigated DCE parameters, kep is the most robust to this investigated bias.

Image guided adaptive external beam radiation therapy for cervix cancer: Evaluation of a clinically implemented plan-of-the-day technique.

BACKGROUND: Radiotherapy for cervix cancer is challenging in patients exhibiting large daily changes in the pelvic anatomy, therefore adaptive treatments (ART) have been proposed. The aim of this study was the clinical implementation and subsequent evaluation of plan-of-the-day (POTD)-ART for cervix cancer in supine positioning. The described workflow was based on standard commercial equipment and current quality assurance (QA) methods. MATERIALS AND METHODS: A POTD strategy, which employs a VMAT plan library consisting of an empty bladder plan, a full bladder plan and a motion robust backup plan, was developed. Daily adaption was guided by cone beam computed tomography (CBCT) imaging after which the best plan from the library was selected. Sixteen patients were recruited in a clinical study on ART, for nine POTD was applied due to their large organ motion derived from two computed tomography (CT) scans with variable bladder filling. All patients were treated to 45Gy in 25 fractions. Plan selection frequencies over the treatment course were analyzed. Daily doses in the rectum, bladder and cervix-uterus target (CTV-T) were derived and compared to a simulated non-adapted treatment (non-ART), which employed the robust plan for each fraction. Additionally, the adaption consistency was determined by repeating the plan selection procedure one month after treatment by a group of experts. ART-specific QA methods are presented. RESULTS: 225 ART fractions with CBCTs were analyzed. The empty bladder plan was delivered in 49% of the fractions in the first treatment week and this number increased to 78% in the fifth week. The daily coverage of the CTV-T was equivalent between ART and the non-ART simulation, while the daily total irradiated volume V42.75Gy (95% of prescription dose) was reduced by a median of 87cm3. The median delivered V42.75Gy was 1782cm3. Daily delivered doses (V42.75Gy, V40Gy, V30G) to the organs at risk were statistically significantly reduced by ART, with a median difference in daily V42.75Gy in rectum and bladder of 3.2% and 1.1%, respectively. The daily bladder V42.75Gy and V40Gy were decreased by more than 10 percent points in 30% and 24% of all fractions, respectively, through ART. The agreement between delivered plans and retrospective expert-group plan selections was 84%. CONCLUSION: A POTD-ART technique for cervix cancer was successfully and safely implemented in the clinic and evaluated. Improved normal tissue sparing compared to a simulated non-ART treatment could be demonstrated. Future developments should focus on commercial automated software solutions to allow for a more widespread adoption and to keep the increased workload manageable.

Changes in Tumor Biology During Chemoradiation of Cervix Cancer Assessed by Multiparametric MRI and Hypoxia PET.

PURPOSE: Imaging biomarkers assessed with magnetic resonance imaging (MRI) and/or positron emission tomography (PET) enable non-invasive tumor characterization in cervix cancer patients. We investigated the spatio-temporal stability of hypoxia, perfusion, and the cell density of tumors over time by repetitive imaging prior to, during, and after radio-chemotherapy. PROCEDURES: Thirteen patients were included in this prospective study. The imaging protocol included the following: [18F]fluoromisonidazole ([18F]FMISO)-PET/x-ray computed tomography (CT) and multiparametric (mp)-MRI at four time-points (TP): baseline (BL); and weeks 2 (TP1), 5 (TP2), and 19 after treatment start (follow-up FU). Complete datasets for six patients could be assessed for tumor volume, enhancement kinetics, diffusivity, and [18F]FMISO-avidity (P1-P6). In addition, two patients completed all PET/CT examinations (P7-P8) but not all MR scans; however, one of them had no hypoxia (P8). Descriptive statistics, correlations, and voxel-by-voxel analysis were performed. For various, independent reasons, five patients could not complete the study according to the protocol with all imaging sequences. RESULTS: Median tumor ADCs (in ×10-3 mm2/s) were 0.99 ± 0.10 at BL, 1.20 ± 0.12 at TP1, 1.33 ± 0.14 at TP2, and 1.38 ± 0.21 at FU. The median TBRpeak (tumor-to-background) was 2.7 ± 0.8 at BL, 1.6 ± 0.2 at TP1, 1.8 ± 0.3 at TP2, and 1.7 ± 0.3 at FU. The voxel-by-voxel analysis of the [18F]FMISO uptake at BL and TP1 showed no correlation. Between TP2 and TP1 and FU and TP2, weak correlations were found for two patients. CONCLUSIONS: Longitudinal mp-MR and PET imaging enables the in vivo tumor characterization over time. While perfusion and cell density decreased, there was a non-uniform change of hypoxia observed during radiotherapy. To assess the potential impact with regard to more personalized treatment approaches, hypoxia imaging-based dose painting for cervix cancer requires further research.

Impact of hybrid PET/MR technology on multiparametric imaging and treatment response assessment of cervix cancer.

BACKGROUND AND PURPOSE: Multimodal tissue characterization by combined MRI and PET has high clinical potential in the context of sub-target definition for dose painting and response assessment but its clinical exploration is yet limited. The aim of this study was to prove the potential and feasibility of hybrid PET/MRI to non-invasively measure tumor hypoxia, perfusion and microstructure at one stop in tumors of the uterine cervix during chemoradiotherapy. MATERIAL AND METHODS: Ten cervix cancer patients were subjected to simultaneous multiparametric PET/MRI with [18F]fluoromisonidazole ([18F]FMISO). Imaging was scheduled before, twice during and after chemoradiotherapy. Intra- and inter-time point analyses of the extracted parameters (i.e. ADC, Ktrans, ABrix, [18F]FMISO-tumor to background ratio (TBR)) were performed. The [18F]FMISO uptake- and ADC-spatio-temporal changes were assessed. RESULTS: Patient averaged ADC values increased from baseline to follow up (1.03 ±â€¯0.11/1.30 ±â€¯0.13 × 10-3 mm2/s), while the TBR decreased (1.73 ±â€¯0.24/1.36 ±â€¯0.19), Ktrans dropped over time (0.17 ±â€¯0.05/0.05 ±â€¯0.05 min-1); for all above p < 0.05. None of these parameters correlated significantly on a voxel-by-voxel basis. Low-ADC regions spatially varied over time. There was pronounced reduction of the [18F]FMISO-avid volumes during treatment. CONCLUSIONS: The suggested hybrid PET/MRI protocol to non-invasively investigate tumor hypoxia, perfusion and microstructure at one stop was feasible, revealing spatio-temporal response patterns that could be utilized for comprehensive sub-target definition for dose painting and response assessment.