Soy lecithin: A beneficial substance for adjusting the ADC in aqueous solutions to the values of biological tissues.

PURPOSE: To test soy lecithin as a substance added to water for the construction of MRI phantoms with tissue-like diffusion coefficients. The performance of soy lecithin was assessed for the useable range of adjustable ADC values, the degree of non-Gaussian diffusion, simultaneous effects on relaxation times, and spectral signal properties. METHODS: Aqueous soy lecithin solutions of different concentrations (0%, 0.5%, 1%, 2%, 3% …, 10%) and soy lecithin-agar gels were prepared and examined on a 3 Tesla clinical scanner at 18.5° ± 0.5°C. Echoplanar sequences (b values: 0-1000/3000 s/mm2 ) were applied for ADC measurements. Quantitative relaxometry and MRS were performed for assessment of T1 , T2 , and detectable spectral components. RESULTS: The presence of soy lecithin significantly restricts the diffusion of water molecules and mimics the nearly Gaussian nature of diffusion observed in tissue (for b values <1000 s/mm2 ). ADC values ranged from 2.02 × 10-3  mm2 /s to 0.48 × 10-3  mm2 /s and cover the entire physiological range reported on biological tissue. Measured T1 /T2 values of pure lecithin solutions varied from 2685/2013 to 668/133 ms with increasing concentration. No characteristic signals of soy lecithin were observed in the MR spectrum. The addition of agar to the soy lecithin solutions allowed T2 values to be well adjusted to typical values found in parenchymal tissue without affecting the soy lecithin-controlled ADC value. CONCLUSION: Soy lecithin is a promising substance for the construction of diffusion phantoms with tissue-like ADC values. It provides several advantages over previously proposed substances, in particular a wide range of adjustable ADC values, the lack of additional 1 H-signals, and the possibility to adjust ADC and T2 values (by adding agar) almost independently of each other.

Machine learning identifies multi-parametric functional PET/MR imaging cluster to predict radiation resistance in preclinical head and neck cancer models.

PURPOSE: Tumor hypoxia and other microenvironmental factors are key determinants of treatment resistance. Hypoxia positron emission tomography (PET) and functional magnetic resonance imaging (MRI) are established prognostic imaging modalities to identify radiation resistance in head-and-neck cancer (HNC). The aim of this preclinical study was to develop a multi-parametric imaging parameter specifically for focal radiotherapy (RT) dose escalation using HNC xenografts of different radiation sensitivities. METHODS: A total of eight human HNC xenograft models were implanted into 68 immunodeficient mice. Combined PET/MRI using dynamic [18F]-fluoromisonidazole (FMISO) hypoxia PET, diffusion-weighted (DW), and dynamic contrast-enhanced MRI was carried out before and after fractionated RT (10 × 2 Gy). Imaging data were analyzed on voxel-basis using principal component (PC) analysis for dynamic data and apparent diffusion coefficients (ADCs) for DW-MRI. A data- and hypothesis-driven machine learning model was trained to identify clusters of high-risk subvolumes (HRSs) from multi-dimensional (1-5D) pre-clinical imaging data before and after RT. The stratification potential of each 1D to 5D model with respect to radiation sensitivity was evaluated using Cohen's d-score and compared to classical features such as mean/peak/maximum standardized uptake values (SUVmean/peak/max) and tumor-to-muscle-ratios (TMRpeak/max) as well as minimum/valley/maximum/mean ADC. RESULTS: Complete 5D imaging data were available for 42 animals. The final preclinical model for HRS identification at baseline yielding the highest stratification potential was defined in 3D imaging space based on ADC and two FMISO PCs ([Formula: see text]). In 1D imaging space, only clusters of ADC revealed significant stratification potential ([Formula: see text]). Among all classical features, only ADCvalley showed significant correlation to radiation resistance ([Formula: see text]). After 2 weeks of RT, FMISO_c1 showed significant correlation to radiation resistance ([Formula: see text]). CONCLUSION: A quantitative imaging metric was described in a preclinical study indicating that radiation-resistant subvolumes in HNC may be detected by clusters of ADC and FMISO using combined PET/MRI which are potential targets for future functional image-guided RT dose-painting approaches and require clinical validation.

Value of PET imaging for radiation therapy.

This comprehensive review written by experts in their field gives an overview on the current status of incorporating positron emission tomography (PET) into radiation treatment planning. Moreover, it highlights ongoing studies for treatment individualisation and per-treatment tumour response monitoring for various primary tumours. Novel tracers and image analysis methods are discussed. The authors believe this contribution to be of crucial value for experts in the field as well as for policy makers deciding on the reimbursement of this powerful imaging modality.

PET/MRI and genetic intrapatient heterogeneity in head and neck cancers.

PURPOSE: The relation between functional imaging and intrapatient genetic heterogeneity remains poorly understood. The aim of our study was to investigate spatial sampling and functional imaging by FDG-PET/MRI to describe intrapatient tumour heterogeneity. METHODS: Six patients with oropharyngeal cancer were included in this pilot study. Two tumour samples per patient were taken and sequenced by next-generation sequencing covering 327 genes relevant in head and neck cancer. Corresponding regions were delineated on pretherapeutic FDG-PET/MRI images to extract apparent diffusion coefficients and standardized uptake values. RESULTS: Samples were collected within the primary tumour (n = 3), within the primary tumour and the involved lymph node (n = 2) as well as within two independent primary tumours (n = 1). Genetic heterogeneity of the primary tumours was limited and most driver gene mutations were found ubiquitously. Slightly increasing heterogeneity was found between primary tumours and lymph node metastases. One private predicted driver mutation within a primary tumour and one in a lymph node were found. However, the two independent primary tumours did not show any shared mutations in spite of a clinically suspected field cancerosis. No conclusive correlation between genetic heterogeneity and heterogeneity of PET/MRI-derived parameters was observed. CONCLUSION: Our limited data suggest that single sampling might be sufficient in some patients with oropharyngeal cancer. However, few driver mutations might be missed and, if feasible, spatial sampling should be considered. In two independent primary tumours, both lesions should be sequenced. Our data with a limited number of patients do not support the concept that multiparametric PET/MRI features are useful to guide biopsies for genetic tumour characterization.

Target miss using PTV-based IMRT compared to robust optimization via coverage probability concept in prostate cancer.

Purpose: Cure- and toxicity rates of prostate IGRT can both be affected by ill-chosen planning target volume (PTV) margins. For dose-escalated prostate radiotherapy, we studied the potential for organ at risk (OAR) sparing and compensation of prostate motion with robust plan optimization using the coverage probability (CovP) concept compared to conventional PTV-based IMRT.Material and methods: We evaluated plan quality of CovP-plans for 27 intermediate risk prostate cancer patients treated in a prospective study (78 Gy/39 fractions). Clinical target volume (CTV) and OARs were contoured on three separate CTs to capture movement and deformation. To define the internal target volume (ITV), the union of CTV1-3 was encompassed by an isotropic margin of 7 mm for the planning process. CovP-dose distribution is optimized considering weight factors for IMRT constraints derived from probabilities of systematic organ displacement in the three CTs. CovP-dose volume histograms (DVHs) were compared with additionally calculated conventional PTV-based IMRT plans. PTV-based IMRT was planned on one-single CT with an isotropically expanded CTV to generate the PTV (i.e., CTV1 + 7mm) and was evaluated on the two other CTs.Results: The CovP-concept showed higher robustness in target volume coverage. Target miss was frequently observed with PTV-based IMRT, resulting in cold spots until 70 Gy with the CovP-concept. The target dose at 74 Gy was comparable, while further the dose-escalation (75-78 Gy) was improved with PTV-based IMRT. However, dose-escalation with PTV-based IMRT was associated with increased OAR-doses, especially in high-dose areas.Conclusions: Probabilistic dose-escalated IMRT was feasible in this prospective study. Comparison of the CovP-concept with PTV-based IMRT revealed superiority with regard to target-coverage and sparing of OARs. The CovP-concept implements a robust plan optimization strategy for organ deformation and motions and could, therefore, serve as a less demanding compromise on the way to adaptive IGRT avoiding daily time-consuming re-planning. SUMMARYWe evaluated the robustness of coverage probability (CovP)-based IMRT plans within a prospective study for prostate cancer radiotherapy. The treatment plans were compared with newly calculated conventional PTV-based IMRT plans. We were able to show that CovP led to a clearly more robust target coverage by avoiding hot spots at OARs compared to conventional PTV-based IMRT. In addition, negative consequences of an inflated PTV can be ameliorated by a more relaxed CovP-based dose prescription.

Comparison of treatment plans for a high-field MRI-linac and a conventional linac for esophageal cancer.

PURPOSE: To compare radiotherapy treatments plans in esophageal cancer calculated for a high-field magnetic resonance imaging (MRI)-linac with plans for a conventional linac. MATERIALS AND METHODS: Ten patients with esophageal squamous cell carcinomas were re-planned retrospectively using the research version of Monaco (V 5.19.03, Elekta AB, Stockholm, Sweden). Intensity modulated radiotherapy (IMRT) plans with a nine-field step-and-shoot technique and two-arc volumetric modulated arc therapy (VMAT) plans were created for the Elekta MRI-linac and a conventional linac, respectively. The prescribed dose was 60 Gy to the primary tumor (PTV60) and 50 Gy to elective volumes (PTV50). Plans were optimized for optimal coverage of the 60 Gy volume and compared using dose-volume histogram parameters. RESULTS: All calculated treatment plans met predefined criteria for target volume coverage and organs at risk dose both for MRI-linac and conventional linac. Plans for the MRI-linac had a lower number of segments and monitor units. No significant differences between both plans were seen in terms of V20Gy of the lungs and V40Gy of the heart with slightly higher mean doses to the heart (14.0 Gy vs. 12.5 Gy) and lungs (12.8 Gy vs. 12.2 Gy). CONCLUSION: Applying conventional target volume and margin concepts as well as dose-fractionation prescription reveals clinically acceptable dose distributions using hybrid MRI-linac in its current configuration compared to standard IMRT/VMAT. This represents an important prerequisite for future studies to investigate the clinical benefit of MRI-guided radiotherapy exploiting the conceptional advantages such as reduced margins, plan adaptation and biological individualization and hypofractionation.

Radiogenomics in head and neck cancer: correlation of radiomic heterogeneity and somatic mutations in TP53, FAT1 and KMT2D.

PURPOSE: Genetic tumour profiles and radiomic features can be used to complement clinical information in head and neck squamous cell carcinoma (HNSCC) patients. Radiogenomics imply the potential to investigate complementarity or interrelations of radiomic and genomic features, and prognostic factors might be determined. The aim of our study was to explore radiogenomics in HNSCC. METHODS: For 20 HNSCC patients treated with primary radiochemotherapy, next-generation sequencing (NGS) of tumour and corresponding normal tissue was performed. In total, 327 genes were investigated by panel sequencing. Radiomic features were extracted from computed tomography data. A hypothesis-driven approach was used for radiogenomic correlations of selected image-based heterogeneity features and well-known driver gene mutations in HNSCC. RESULTS: The most frequently mutated driver genes in our cohort were TP53 (involved in cell cycle control), FAT1 (Wnt signalling, cell-cell contacts, migration) and KMT2D (chromatin modification). Radiomic features of heterogeneity did not correlate significantly with somatic mutations in TP53 or KMT2D. However, somatic mutations in FAT1 and smaller primary tumour volumes were associated with reduced radiomic intra-tumour heterogeneity. CONCLUSION: The landscape of somatic variants in our cohort is well in line with previous reports. An association of somatic mutations in FAT1 with reduced radiomic tumour heterogeneity could potentially elucidate the previously described favourable outcomes of these patients. Larger studies are needed to validate this exploratory data in the future.

Automatic replanning of VMAT plans for different treatment machines: A template-based approach using constrained optimization.

PURPOSE: To investigate a new automatic template-based replanning approach combined with constrained optimization, which may be highly useful for a rapid plan transfer for planned or unplanned machine breakdowns. This approach was tested for prostate cancer (PC) and head-and-neck cancer (HNC) cases. METHODS: The constraints of a previously optimized volumetric modulated arc therapy (VMAT) plan were used as a template for automatic plan reoptimization for different accelerator head models. All plans were generated using the treatment planning system (TPS) Hyperion. Automatic replanning was performed for 16 PC cases, initially planned for MLC1 (4 mm MLC) and reoptimized for MLC2 (5 mm) and MLC3 (10 mm) and for 19 HNC cases, replanned from MLC2 to MLC3. EUD, Dmean, D2%, and D98% were evaluated for targets; for OARs EUD and D2% were analyzed. Replanning was considered successful if both plans fulfilled equal constraints. RESULTS: All prostate cases were successfully replanned. The mean relative target EUD deviation was -0.15% and -0.57% for replanning to MLC2 and MLC3, respectively. OAR sparing was successful in all cases. Replanning of HNC cases from MLC2 to MLC3 was successful in 16/19 patients with a mean decrease of -0.64% in PTV60 EUD. In three cases target doses were substantially decreased by up to -2.58% (PTV60) and -3.44% (PTV54), respectively. Nevertheless, OAR sparing was always achieved as planned. CONCLUSIONS: Automatic replanning of VMAT plans for a different treatment machine by using pre-existing constraints as a template for a reoptimization is feasible and successful in terms of equal constraints.

Voxel-wise correlation of functional imaging parameters in HNSCC patients receiving PET/MRI in an irradiation setup.

PURPOSE: The purpose of this study was to demonstrate the feasibility of voxel-wise multiparametric characterization of head and neck squamous cell carcinomas (HNSCC) using hybrid multiparametric magnetic resonance imaging and positron emission tomography with [18F]-fluorodesoxyglucose (FDG-PET/MRI) in a radiation treatment planning setup. METHODS: Ten patients with locally advanced HNSCC were examined with a combined FDG-PET/MRI in an irradiation planning setup. The multiparametric imaging protocol consisted of FDG-PET, T2-weighted transverse short tau inversion recovery sequence (STIR) and diffusion-weighted MRI (DWI). Primary tumours were manually segmented and quantitative imaging parameters were extracted. PET standardized uptake values (SUV) and DWI apparent diffusion coefficients (ADC) were correlated on a voxel-wise level. RESULTS: Images acquired in this specialised radiotherapy planning setup achieved good diagnostic quality. Median tumour volume was 4.9 [1.1-42.1] ml. Mean PET SUV and ADC of the primary tumours were 5 ± 2.5 and 1.2 ± 0.3 10-3 mm2/s, respectively. In voxel-wise correlation between ADC values and corresponding FDG SUV of the tumours, a significant negative correlation was observed (r = -0.31 ± 0.27, p < 0.05). CONCLUSION: Multiparametric voxel-wise characterization of HNSCC is feasible using combined PET/MRI in a radiation planning setup. This technique may provide novel insights into tumour biology with regard to radiation therapy in the future.

Overlap of highly FDG-avid and FMISO hypoxic tumor subvolumes in patients with head and neck cancer.

BACKGROUND: PET imaging may be used to personalize radiotherapy (RT) by identifying radioresistant tumor subvolumes for RT dose escalation. Using the tracers [18F]-fluorodeoxyglucose (FDG) and [18F]-fluoromisonidazole (FMISO), different aspects of tumor biology can be visualized. FDG depicts various biological aspects, e.g., proliferation, glycolysis and hypoxia, while FMISO is more hypoxia specific. In this study, we analyzed size and overlap of volumes based on the two markers for head-and-neck cancer patients (HNSCC). MATERIAL AND METHODS: Twenty five HNSCC patients underwent a CT scan, as well as FDG and dynamic FMISO PET/CT prior to definitive radio-chemotherapy in a prospective FMISO dose escalation study. Three PET-based subvolumes of the primary tumor (GTVprim) were segmented: a highly FDG-avid volume VFDG, a hypoxic volume on the static FMISO image acquired four hours post tracer injection (VH) and a retention/perfusion volume (VM) using pharmacokinetic modeling of dynamic FMISO data. Absolute volumes, overlaps and distances to agreement (DTA) were evaluated. RESULTS: Sizes of PET-based volumes and the GTVprim are significantly different (GTVprim>VFDG>VH >VM; p < .05). VH is covered by VFDG or DTAs are small (mean coverage 74.4%, mean DTA 1.4 mm). Coverage of VM is less pronounced. With respect to VFDG and VH, the mean coverage is 48.7% and 43.1% and the mean DTA is 5.3 mm and 6.3 mm, respectively. For two patients, DTAs were larger than 2 cm. CONCLUSIONS: Hypoxic subvolumes from static PET imaging are typically covered by or in close proximity to highly FDG-avid subvolumes. Therefore, dose escalation to FDG positive subvolumes should cover the static hypoxic subvolumes in most patients, with the disadvantage of larger volumes, resulting in a higher risk of dose-limiting toxicity. Coverage of subvolumes from dynamic FMISO PET is less pronounced. Further studies are needed to explore the relevance of mismatches in functional imaging.

Geometric analysis of loco-regional recurrences in relation to pre-treatment hypoxia in patients with head and neck cancer.

INTRODUCTION: A previous pattern-of-failure study has suggested that up to 50% of the loco-regional failures (LRF) in head and neck squamous cell carcinoma (HNSCC) occur outside the initial hypoxic volume determined by [18F]-fluoromisonidazole-PET ([18F]-FMISO-PET). The aim of the present analysis was to correlate spatial patterns of failure with respect to the pretherapeutic dynamic [18F]-FMISO-PET/CT in HNSCC after radiochemotherapy (RCT). MATERIAL AND METHODS: Within a running phase 2 trial using [18F]-FMISO-PET imaging prior to RCT in HNSCC patients (n = 54), we have observed so far 11 LRF with a minimum follow-up of 12 months. For nine patients, LRF imaging (CT or [18F]-FDG-PET/CT) for pattern-of-failure analysis was available. Analysis included the static 4-h hypoxic subvolume (VH) as well as a M-parameter volume (VM), which is derived from modeling of dynamic PET. Deformable image registration of the CT scan with the recurrent tumor to the pre-treatment [18F]-FMISO-PET/CT and the planning CT was done to quantify the hypoxic subvolumes compared to the recurrent tumor volume. Moreover, a point-of-origin analysis was performed. RESULTS: A total of five local, two regional and two loco-regional recurrences were detected. After deformable image registration of the CT scan with the recurrent tumor to the pre-treatment [18F]-FMISO-PET/CT and the planning CT, a significant overlap of the recurrence volume with [18F]-FMISO-positive subvolumes in the initial gross tumor volume (GTV) was observed. Median overlap of 40.2%, range 9.4-100.0%, for VH and 49.0%, range 4.4-96.4%, for VM was calculated. The point-of-origin analysis showed median distances of 0.0 mm, range 0.0-11.3 mm to VH and 8.6 mm, range 0.0-15.5 mm to VM, respectively. CONCLUSIONS: Our data suggest that loco-regional recurrences after RCT originate from the initial GTV (primary tumor and/or lymph node metastases) containing hypoxic subvolumes, which supports the concept of hypoxia imaging-based dose escalation.

FDG and Beyond.

Although many PET tracers are in use, FDG still is the most widely used in clinical oncology practice. FDG therefore deserves an in-depth discussion, which is even more interesting because of the huge increase in the molecular biology of glucose metabolism. Obviously, other tracers are of increasing importance as well, and these will be discussed in short.

Robustness of quantitative hypoxia PET image analysis for predicting local tumor control.

BACKGROUND: Previous studies suggested the maximum tumor to background ratio (TBRmax) in FMISO PET images as a potentially predictive parameter for local control after radio-chemotherapy (CRT) in head and neck squamous cell carcinomas (HNSCC). However, different TBRmax thresholds for stratification were reported, implying that a common threshold cannot readily be used among different institutions without the risk of reducing prediction accuracy. Therefore, this study investigated the robustness of using a common pre-defined TBRmax, simulating a multicenter clinical trial. MATERIAL AND METHODS: FMISO PET/CT was performed four hours post-injection in 22 patients with advanced HNSCC in a phase II FMISO dose escalation study. PET background regions of interest (ROIs) were manually defined in deep neck muscles. TBRmax was calculated as the mean of the highest-valued voxels within the high risk RT planning target volume. Its predictive power with respect to local control was tested, classifying patients using median TBRmax as threshold. The influence of systematically varying quantification between institutions was studied in silico by applying offsets of ± 10% and ± 20% to the TBRmax of all patients, while the threshold remained constant. The effect was analyzed using a receiver operating characteristic (ROC). True positive and false positive rates (TPR/FPR) as well as positive and negative predictive values (PPV/NPV) were evaluated. RESULTS: For the reference condition without an offset the median TBRmax was 2.0 (1.4-3.5). Patients were classified using this threshold and TPR = 0.7, FPR = 0.4, PPV = 0.5 and NPV = 0.8 were observed. Accuracy declined with increasing offsets. Negative offsets of -10% and -20% resulted in TPR = 0.43 and 0.14, FPR = 0.20 and 0.13, PPV = 0.50 and 0.33 and NPV = 0.75 and 0.68, respectively. Positive offsets of + 10% and + 20% resulted in TPR = 1.00 and 1.00, FPR = 0.53 and 0.67, PPV = 0.47 and 0.41 and NPV = 1.00 and 1.00, respectively. CONCLUSIONS: Using a common pre-defined TBRmax threshold in multicenter trials requires careful standardization and harmonization of all steps from patient preparation to image analysis. Our results indicate that TBRmax should deviate less than 10% from reference conditions (absolute value in this dataset ± 0.2). This conclusion likely applies to all low contrast nitroimidazole hypoxia PET tracers.

Comparison of [18F]-FMISO, [18F]-FAZA and [18F]-HX4 for PET imaging of hypoxia--a simulation study.

BACKGROUND: To investigate the effect of hypoxia tracer properties on positron emission tomography (PET) image quality for three tracers [18F]-fluoromisonidazole (FMISO), [18F]-fluoroazomycinarabinoside (FAZA) and [18F]-flortanidazole (HX4), using mathematical simulations based on microscopic tumor tissue sections. MATERIAL AND METHODS: Oxygen distribution and tracer binding was mathematically simulated on immunohistochemically stained cross-sections of tumor xenografts. Tracer diffusion properties were determined based on available literature. Blood activity and clearance over a four-hour period post-injection (p.i.) were derived from clinical dynamic PET scans of patients suffering from head and neck or bronchial cancer. Simulations were performed both for average patient blood activities and for individual patients, and image contrast between normoxic and hypoxic tissue areas was determined over this four-hour period p.i. RESULTS: On average, HX4 showed a six-fold higher clearance than FMISO and an almost three-fold higher clearance than FAZA based on the clinical PET data. The absolute variation in clearance was significantly higher for HX4 than for FMISO (standard deviations of 5.75 *10-5 s-1 vs. 1.55 *10-5 s-1). The absolute tracer activity in these scans at four hours p.i. was highest for FMISO and lowest for HX4. Simulated contrast at four hours p.i. was highest for HX4 (2.39), while FMISO and FAZA were comparable (1.67 and 1.75, respectively). Variations in contrast of 7-11% were observed for each tracer depending on the vascularization patterns of the chosen tissue. Higher variations in clearance for HX4 resulted in an increased inter-patient variance in simulated contrast at four hours p.i. CONCLUSIONS: In line with recent experimental and clinical data, the results suggest that HX4 is a promising new tracer that provides high image contrast four hours p.i., though inter-patient variance can be very high. Nevertheless, the widely used tracer FMISO provides a robust and reproducible signal four hours p.i., but with a lower contrast. The simulations revealed tracer clearance to be the key factor in determining image contrast.

Experimental characterization of four ionization chamber types in magnetic fields including intra-type variation.

Background and purpose: For dosimetry in magnetic resonance (MR) guided radiotherapy, assessing the magnetic field correction factors of air-vented ionization chambers is crucial. Novel MR-optimized chambers reduce MR-imaging artefacts, enhancing their quality assurance utility. This study aimed to characterize two new MR-optimized ionization chambers with sensitive volumes of 0.07 and 0.016 cm3 regarding magnetic field correction factors and intra-type variation and compare them to their conventional counterparts. Material and methods: Five chambers of each type were evaluated in a water phantom, using a clinical linear accelerator and an electromagnet, as well as a 1.5 T MR-linac system. The magnetic field correction factor kB→,Q, addressing the change of response caused by a magnetic field, was assessed together with its intra-type variation. MR-optimized and conventional chambers were compared using a Mann-Whitney U-Test. Results: Considering 1.5 T and a perpendicular chamber orientation, we observed significant differences in the magnetic field-induced change in chamber reading between the two 0.016 cm3 chamber versions (p = 0.03). For a 7 MV beam, MR-optimized chambers (0.016/0.07 cm3) showed kB→,Q values of 1.0426(66) and 1.0463(44), compared to 1.0319(53) and 1.0480(41) of their conventional counterparts. In anti-parallel orientation, kB→,Q was 1.0012(69) and 0.9863(49) for the MR-optimized chambers. The average intra-type variation of kB→,Q over all chamber types was 0.3%. Conclusion: Magnetic field correction factors were successfully determined for four ionization chamber types, including two new MR-optimized versions, allowing their use in MR-linac absolute dosimetry. Evaluation of the intra-type variation enabled the assessment of their contribution to the uncertainty of tabulated kB→,Q.

MRI-Guided Adaptive Radiation Therapy.

Magnetic resonance imaging-guided radiation therapy (MRIgRT) has improved soft tissue contrast over computed tomography (CT) based image-guided RT. Superior visualization of the target and surrounding radiosensitive structures has the potential to improve oncological outcomes partly due to safer dose-escalation and adaptive planning. In this review, we highlight the workflow of adaptive MRIgRT planning, which includes simulation imaging, daily MRI, identifying isocenter shifts, contouring, plan optimization, quality control, and delivery. Increased utilization of MRIgRT will depend on addressing technical limitations of this technology, while addressing treatment efficacy, cost-effectiveness, and workflow training.

Reproducibility of diffusion-weighted magnetic resonance imaging in head and neck cancer assessed on a 1.5 T MR-Linac and comparison to parallel measurements on a 3 T diagnostic scanner.

BACKGROUND AND PURPOSE: Before quantitative imaging biomarkers (QIBs) acquired with magnetic resonance imaging (MRI) can be used for interventional trials in radiotherapy (RT), technical validation of these QIBs is necessary. The aim of this study was to assess the reproducibility of apparent diffusion coefficient (ADC) values, derived from diffusion-weighted (DW) MRI, in head and neck cancer using a 1.5 T MR-Linac (MRL) by comparison to a 3 T diagnostic scanner (DS). MATERIAL AND METHODS: DW-MRIs were acquired on MRL and DS for 15 head and neck cancer patients before RT and in week 2 and rigidly registered to the planning computed tomography. Mean ADC values were calculated for submandibular (SG) and parotid (PG) glands as well as target volumes (TV, gross tumor volume and lymph nodes), which were delineated based on computed tomography. Mean absolute ADC differences as well as within-subject coefficient of variation (wCV) and intraclass correlation coefficients (ICCs) were calculated for all volumes of interest. RESULTS: A total of 23 datasets were analyzed. Mean ADC difference (DS-MRL) for SG, PG and TV resulted in 142, 254 and 93·10-6 mm2/s. wCVs/ICCs, comparing MRL and DS, were determined as 13.7 %/0.26, 24.4 %/0.23 and 16.1 %/0.73 for SG, PG and TV, respectively. CONCLUSION: ADC values, measured on the 1.5 T MRL, showed reasonable reproducibility with an ADC underestimation in contrast to the DS. This ADC shift must be validated in further experiments and considered for future translation of QIB candidates from DS to MRL for response adaptive RT.

Full daily re-optimization improves plan quality during online adaptive radiotherapy.

Background and purpose: Daily online treatment plan adaptation requires a fast workflow and planning process. Current online planning consists of adaptation of a predefined reference plan, which might be suboptimal in cases of large anatomic changes. The aim of this study was to investigate plan quality differences between the current online re-planning approach and a complete re-optimization. Material and methods: Magnetic resonance linear accelerator reference plans for ten prostate cancer patients were automatically generated using particle swarm optimization (PSO). Adapted plans were created for each fraction using (1) the current re-planning approach and (2) full PSO re-optimization and evaluated overall compliance with institutional dose-volume criteria compared to (3) clinically delivered fractions. Relative volume differences between reference and daily anatomy were assessed for planning target volumes (PTV60, PTV57.6), rectum and bladder and correlated with dose-volume results. Results: The PSO approach showed significantly higher adherence to dose-volume criteria than the reference approach and clinical fractions (p < 0.001). In 74 % of PSO plans at most one criterion failed compared to 56 % in the reference approach and 41 % in clinical plans. A fair correlation between PTV60 D98% and relative bladder volume change was observed for the reference approach. Bladder volume reductions larger than 50 % compared to the reference plan recurrently decreased PTV60 D98% below 56 Gy. Conclusion: Complete re-optimization maintained target coverage and organs at risk sparing even after large anatomic variations. Re-planning based on daily magnetic resonance imaging was sufficient for small variations, while large variations led to decreasing target coverage and organ-at-risk sparing.

Online Adaptive MR-Guided Ultrahypofractionated Radiotherapy of Prostate Cancer on a 1.5 T MR-Linac: Clinical Experience and Prospective Evaluation.

The use of hypofractionated radiotherapy in prostate cancer has been increasingly evaluated, whereas accumulated evidence demonstrates comparable oncologic outcomes and toxicity rates compared to normofractionated radiotherapy. In this prospective study, we evaluate all patients with intermediate-risk prostate cancer treated with ultrahypofractionated (UHF) MRI-guided radiotherapy on a 1.5 T MR-Linac within our department and report on workflow and feasibility, as well as physician-recorded and patient-reported longitudinal toxicity. A total of 23 patients with intermediate-risk prostate cancer treated on the 1.5 T MR-Linac with a dose of 42.7 Gy in seven fractions (seven MV step-and-shoot IMRT) were evaluated within the MRL-01 study (NCT04172753). The duration of each treatment step, choice of workflow (adapt to shape-ATS or adapt to position-ATP) and technical and/or patient-sided treatment failure were recorded for each fraction and patient. Acute and late toxicity were scored according to RTOG and CTC V4.0, as well as the use of patient-reported questionnaires. The median follow-up was 12.4 months. All patients completed the planned treatment. The mean duration of a treatment session was 38.2 min. In total, 165 radiotherapy fractions were delivered. ATS was performed in 150 fractions, 5 fractions were delivered using ATP, and 10 fractions were delivered using both ATS and ATP workflows. Severe acute bother (G3+) regarding IPS-score was reported in five patients (23%) at the end of radiotherapy. However, this tended to normalize and no G3+ IPS-score was observed later at any point during follow-up. Furthermore, no other severe genitourinary (GU) or gastrointestinal (GI) acute or late toxicity was observed. One-year biochemical-free recurrence survival was 100%. We report the excellent feasibility of UHF MR-guided radiotherapy for intermediate-risk prostate cancer patients and acceptable toxicity rates in our preliminary study. Randomized controlled studies with long-term follow-up are warranted to detect possible advantages over current state-of-the-art RT techniques.