ART for head and neck patients: On the difference between VMAT and IMPT.

UNLABELLED: Anatomical changes in the head-and-neck (H&N) region during the course of treatment can cause deteriorated dose distributions. Different replanning strategies were investigated for volumetric modulated arc therapy (VMAT) and intensity-modulated proton therapy (IMPT). MATERIAL AND METHODS: For six H&N patients two repeated computed tomography (CT) and magnetic resonance (MR) (CT1/MR1 at week 2 and CT2/MR2 at week 4) scans were acquired additionally to the initial planning CT/MR. Organs-at-risk (OARs) and three targets (CTV70Gy, CTV63Gy, CTV56Gy) were delineated on MRs and transferred to respective CT data set. Simultaneously integrated boost plans were created using VMAT (two arcs) and IMPT (four beams). To assess the need of replanning the initial VMAT and IMPT plans were recalculated on repeated CTs. Furthermore, VMAT and IMPT plans were replanned on the repeated CTs. A Demon algorithm was used for deformable registration of the repeated CTs with the initial CT and utilized for dose accumulation. Total dose estimations were performed to compare ART versus standard treatment strategies. RESULTS: Dosimetric evaluation of recalculated plans on CT1 and CT2 showed increasing OAR doses for both, VMAT and IMPT. The target coverage of recalculated VMAT plans was considered acceptable in three cases, while for all IMPT plans it dropped. Adaptation of the treatment reduced D2% for brainstem by 6.7 Gy for VMAT and by 8 Gy for IMPT, for particular patients. These D2% reductions were reaching 9 Gy and 14 Gy for the spinal cord. ART improved target dose homogeneity, especially for protons, i.e. D2% decreased by up to 8 Gy while D98% increased by 1.2 Gy. CONCLUSION: ART showed benefits for both modalities. However, as IMPT is more conformal, the magnitude of dosimetric changes was more pronounced compared to VMAT. Large anatomic variations had a severe impact on treatment plan quality for both VMAT and IMPT. ART is justified in those cases irrespective of treatment modalities.

Attenuation correction of a flat table top for radiation therapy in hybrid PET/MR using CT- and 68Ge/68Ga transmission scan-based µ-maps.

Hybrid PET/MR offers new opportunities in radiation oncology for tissue/tumour characterisation and response assessment. Attenuation correction (AC) is an important issue especially in the presence of immobilization devices and flat table tops (FTT). The goal of this study was to compare two methods of AC using CT- and 68Ge/68Ga transmission scan-based attenuation maps (µ-maps) for a custom-designed FTT. Measurements were performed in the mMR PET/MR and TrueV PET/CT Biograph Siemens scanners with three different phantoms, namely the Siemens MR-QA, a cubic canister and the NEMA IEC body phantom. The study revealed that the MR image quality is not hampered by the presence of the FTT. For cubic canister applying the scanner's inherent AC alone resulted in inaccuracies in PET images, with up to -4.0% underestimation of the activity. The mean NEMA sphere activity measurements without FTT, agreed within 3.5% with the respective inserted activity. Placing the FTT in the PET/MR scanner resulted in a difference to the injected activity of 4.5% when the table was not corrected for. By introducing the µ-maps the discrepancy between the used activity and the measurements decreased down to 2.6%. To improve the AC of the FTT the creation of a dedicated µ-map was necessary while the CT-based µ-map performed equally good as the source transmission scan-based one.

Sequential [18F]FDG-[18F]FMISO PET and Multiparametric MRI at 3T for Insights into Breast Cancer Heterogeneity and Correlation with Patient Outcomes: First Clinical Experience.

The aim of this study was to assess whether sequential multiparametric 18[F]fluoro-desoxy-glucose (18[F]FDG)/[18F]fluoromisonidazole ([18F]FMISO) PET-MRI in breast cancer patients is possible, facilitates information on tumor heterogeneity, and correlates with prognostic indicators. In this pilot study, IRB-approved, prospective study, nine patients with ten suspicious breast lesions (BIRADS 5) and subsequent breast cancer diagnosis underwent sequential combined [18F]FDG/[18F]FMISO PET-MRI. [18F]FDG was used to assess increased glycolysis, while [18F]FMISO was used to detect tumor hypoxia. MRI protocol included dynamic breast contrast-enhanced MRI (DCE-MRI) and diffusion-weighted imaging (DWI). Qualitative and quantitative multiparametric imaging findings were compared with pathological features (grading, proliferation, and receptor status) and clinical endpoints (recurrence/metastases and disease-specific death) using multiple correlation analysis. Histopathology was the standard of reference. There were several intermediate to strong correlations identified between quantitative bioimaging markers, histopathologic tumor characteristics, and clinical endpoints. Based on correlation analysis, multiparametric criteria provided independent information. The prognostic indicators proliferation rate, death, and presence/development of recurrence/metastasis correlated positively, whereas the prognostic indicator estrogen receptor status correlated negatively with PET parameters. The strongest correlations were found between disease-specific death and [18F]FDGmean (R=0.83, p < 0.01) and between the presence/development of metastasis and [18F]FDGmax (R=0.79, p < 0.01), respectively. This pilot study indicates that multiparametric [18F]FDG/[18F]FMISO PET-MRI might provide complementary quantitative prognostic information on breast tumors including clinical endpoints and thus might be used to tailor treatment for precision medicine in breast cancer.

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.

Association between pathology and texture features of multi parametric MRI of the prostate.

The role of multi-parametric (mp)MRI in the diagnosis and treatment of prostate cancer has increased considerably. An alternative to visual inspection of mpMRI is the evaluation using histogram-based (first order statistics) parameters and textural features (second order statistics). The aims of the present work were to investigate the relationship between benign and malignant sub-volumes of the prostate and textures obtained from mpMR images. The performance of tumor prediction was investigated based on the combination of histogram-based and textural parameters. Subsequently, the relative importance of mpMR images was assessed and the benefit of additional imaging analyzed. Finally, sub-structures based on the PI-RADS classification were investigated as potential regions to automatically detect maligned lesions. Twenty-five patients who received mpMRI prior to radical prostatectomy were included in the study. The imaging protocol included T2, DWI, and DCE. Delineation of tumor regions was performed based on pathological information. First and second order statistics were derived from each structure and for all image modalities. The resulting data were processed with multivariate analysis, using PCA (principal component analysis) and OPLS-DA (orthogonal partial least squares discriminant analysis) for separation of malignant and healthy tissue. PCA showed a clear difference between tumor and healthy regions in the peripheral zone for all investigated images. The predictive ability of the OPLS-DA models increased for all image modalities when first and second order statistics were combined. The predictive value reached a plateau after adding ADC and T2, and did not increase further with the addition of other image information. The present study indicates a distinct difference in the signatures between malign and benign prostate tissue. This is an absolute prerequisite for automatic tumor segmentation, but only the first step in that direction. For the specific identified signature, DCE did not add complementary information to T2 and ADC maps.

Advanced Radiation DOSimetry phantom (ARDOS): a versatile breathing phantom for 4D radiation therapy and medical imaging.

A novel breathing phantom was designed for being used in conventional and ion-beam radiotherapy as well as for medical imaging. Accurate dose delivery and patient safety are aimed to be verified for four-dimensional (4D) treatment techniques compensating for breathing-induced tumor motion. The phantom includes anthropomorphic components representing an average human thorax. It consists of real tissue equivalent materials to fulfill the requirements for dosimetric experiments and imaging purposes. The different parts of the torso (lungs, chest wall, and ribs) and the tumor can move independently. Simple regular movements, as well as more advanced patient-specific breathing cycles are feasible while a reproducible setup can be guaranteed. The phantom provides the flexibility to use different types of dosimetric devices and was designed in a way that it is robust, transportable and easy to handle. Tolerance levels and the reliability of the phantom setup were determined in combination with tests on motion accuracy and reproducibility by using infrared optical tracking technology. Different imaging was performed including positron emission tomography imaging, 4D computed tomography as well as real-time in-room imaging. The initial dosimetric benchmarking studies were performed in a photon beam where dose parameters are predictable and the dosimetric procedures well established.

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.

Multiparametric [11C]Acetate positron emission tomography-magnetic resonance imaging in the assessment and staging of prostate cancer.

BACKGROUND: The aim of this study was to evaluate whether MP [11C]Acetate PET-MRI enables an accurate differentiation of benign and malignant prostate tumors as well as local and distant staging. MATERIALS AND METHODS: Fifty-six consecutive patients fulfilling the following criteria were included in this IRB-approved prospective study: elevated PSA levels or suspicious findings at digital rectal examination or TRUS; and histopathological verification. All patients underwent MP [11C]Acetate PET-MRI of the prostate performed on separate scanners with PET/CT using [11C]Acetate and 3T MP MR imaging. Appropriate statistical tests were used to determine diagnostic accuracy, local and distant staging. RESULTS: MP imaging with two MRI parameters (T2w and DWI) achieved the highest sensitivity, specificity, and diagnostic accuracy of 95%, 68.8%, and 88%, with an AUC of 0.82 for primary PCa detection. Neither assessments with a single parameter (AUC, 0.54-0.79), nor different combinations with up to five parameters (AUC, 0.67-0.79) achieved equally good results. MP [11C]Acetate PET-MRI improved local staging with a sensitivity, specificity, and diagnostic accuracy of 100%, 96%, and 97% compared to MRI alone with 72.2%, 100%, and 95.5%. MP [11C]Acetate PET-MRI correctly detected osseous and liver metastases in five patients. CONCLUSIONS: MP [11C]Acetate PET-MRI merges morphologic with functional information, and allows insights into tumor biology. MP [11C]Acetate PET-MRI with two MRI-derived parameters (T2 and DWI) yields the highest diagnostic accuracy. The addition of more parameters does not improve diagnostic accuracy of primary PCa detection. MP [11C]Acetate PET-MRI facilitates improved local and distant staging, providing "one-stop" staging in patients with primary PCa, and therefore has the potential to improve therapy. PATIENT SUMMARY: In this report we investigated MP [11C]Acetate PET-MRI for detection, local and distant staging of prostate cancer. We demonstrate that MP [11C]Acetate PET-MRI with two MRI-derived parameters (T2 and DWI) achieves the best diagnostic accuracy for primary prostate cancer detection and that MP [11C]Acetate PET-MRI enables an improved local and distant staging.

Multiparametric [18F]Fluorodeoxyglucose/ [18F]Fluoromisonidazole Positron Emission Tomography/ Magnetic Resonance Imaging of Locally Advanced Cervical Cancer for the Non-Invasive Detection of Tumor Heterogeneity: A Pilot Study.

OBJECTIVES: To investigate fused multiparametric positron emission tomography/magnetic resonance imaging (MP PET/MRI) at 3T in patients with locally advanced cervical cancer, using high-resolution T2-weighted, contrast-enhanced MRI (CE-MRI), diffusion-weighted imaging (DWI), and the radiotracers [18F]fluorodeoxyglucose ([18F]FDG) and [18F]fluoromisonidazol ([18F]FMISO) for the non-invasive detection of tumor heterogeneity for an improved planning of chemo-radiation therapy (CRT). MATERIALS AND METHODS: Sixteen patients with locally advanced cervix were enrolled in this IRB approved and were examined with fused MP [18F]FDG/ [18F]FMISO PET/MRI and in eleven patients complete data sets were acquired. MP PET/MRI was assessed for tumor volume, enhancement (EH)-kinetics, diffusivity, and [18F]FDG/ [18F]FMISO-avidity. Descriptive statistics and voxel-by-voxel analysis of MRI and PET parameters were performed. Correlations were assessed using multiple correlation analysis. RESULTS: All tumors displayed imaging parameters concordant with cervix cancer, i.e. type II/III EH-kinetics, restricted diffusivity (median ADC 0.80x10-3mm2/sec), [18F]FDG- (median SUVmax16.2) and [18F]FMISO-avidity (median SUVmax3.1). In all patients, [18F]FMISO PET identified the hypoxic tumor subvolume, which was independent of tumor volume. A voxel-by-voxel analysis revealed only weak correlations between the MRI and PET parameters (0.05-0.22), indicating that each individual parameter yields independent information and the presence of tumor heterogeneity. CONCLUSION: MP [18F]FDG/ [18F]FMISO PET/MRI in patients with cervical cancer facilitates the acquisition of independent predictive and prognostic imaging parameters. MP [18F]FDG/ [18F]FMISO PET/MRI enables insights into tumor biology on multiple levels and provides information on tumor heterogeneity, which has the potential to improve the planning of CRT.

Feasibility of dominant intraprostatic lesion boosting using advanced photon-, proton- or brachytherapy.

BACKGROUND AND PURPOSE: Advancements in imaging and dose delivery enable boosting of the dominant intraprostatic lesions (DIL), while maintaining organs-at-risk (OAR) tolerances. This study aimed to assess the feasibility of DIL boosting for volumetric modulated arc therapy (VMAT), intensity modulated proton therapy (IMPT) and high dose rate brachytherapy (HDR-BT). MATERIAL AND METHODS: DILs were defined on multiparametric magnetic resonance imaging and fused with planning CT for twelve patients. VMAT, IMPT and HDR-BT plans were created for each patient with an EQD2(α/ß) DIL aimed at 111.6 Gy, PTV(initial) D(pres) was 80.9 Gy (EBRT) with CTV D90%=81.9 Gy (HDR-BT). Hard dose constraints were applied for OARs. RESULTS: Higher boost doses were achieved with IMPT compared to VMAT, keeping major OAR doses at similar levels. Patient averaged EQD2(α/ß) D50% to DIL were 110.7, 114.2 and 150.1 Gy(IsoE) for VMAT, IMPT and HDR-BT, respectively. Respective rectal wall D(mean) were 30.5±5.0, 16.7±3.6, 9.5±2.5 Gy(IsoE) and bladder wall D(mean) were 21.0±5.5, 15.6±4.3 and 6.3±2.2 Gy(IsoE). CONCLUSIONS: DIL boosting was found to be feasible with all investigated techniques. Although OAR doses were higher than for standard treatment approach, the risk levels were reasonably low. HDR-BT was superior to VMAT and IMPT, both in terms of OAR sparing and DIL boosting.