The increased linear energy transfer (LET) at the end of the Bragg peak causes concern for an elevated and spatially varying relative biological effectiveness (RBE) of proton therapy (PT), often in ...or close to dose-limiting normal tissues. In this study, we investigated dose-averaged LET (LET
) distributions for spot scanning PT of prostate cancer patients using different beam angle configurations. In addition, we derived RBE-weighted (RBE
) dose distributions and related normal tissue complication probabilities (NTCPs) for the rectum and bladder.
A total of 21 spot scanning proton plans were created for each of six patients using a prescription dose of 78 Gy(RBE
), with each plan using two 'mirrored' beams with gantry angles from 110°/250° to 70°/290°, in steps of 2°. Physical dose and LET
distributions were calculated as well as RBE
dose distributions using either RBE = 1.1 or three different variable RBE models. The resulting biological dose distributions were used as input to NTCP models for the rectum and bladder.
For anterior oblique (AO) configurations, the rectum LET
volume and RBE
dose increased with increasing angles off the lateral opposing axis, with the RBE
rectum dose being higher than for all posterior oblique (PO) configurations. For PO configurations, the corresponding trend was seen for the bladder. Using variable RBE models, the rectum NTCPs were highest for the AO configurations with up to 3% for the 80°/280° configuration while the bladder NTCPs were highest for the PO configurations with up to 32% for the 100°/260°. The rectum D
constraint was fulfilled for most patients/configurations when using uniform RBE but not for any patient/configuration with variable RBE models.
Compared to using constant RBE, the variable RBE models predicted increased biological doses to the rectum, bladder and prostate, which in turn lead to substantially higher estimated rectum and bladder NTCPs.
Background: Proton arc therapy may improve physical dose conformity and reduce concerns of elevated linear energy transfer (LET) and relative biological effectiveness (RBE) at the end of the proton ...range, while offering more degrees of freedom for normal tissue sparing. To explore the potential of proton arc therapy, we studied the effect of increasing the number of beams on physical and biologically equivalent dose conformity in the setting of pediatric brain tumors.
Material and methods: A cylindrical phantom (Ø = 150 mm) with central cylindrical targets (Ø = 25 and 30 mm) was planned with increasing number of equiangular coplanar proton beams (from 3 to 36). For four anonymized pediatric brain tumor patients, two 'surrogate' proton arc plans (18 equiangular coplanar or sagittal beams) and a reference plan with 3 non-coplanar beams were constructed. Biologically equivalent doses were calculated using two RBE scenarios: RBE
1.1
; and RBE
LET
, the physical dose weighted by the LET. For both RBE scenarios, dose gradients were assessed, and doses to cognitive brain structures were reported.
Results: Increasing the number of beams resulted in an improved dose gradient and reduced volume exposed to intermediate LET levels, at the expense of increased low-dose and low-LET volumes. Most of the differences between the two RBE scenarios were seen around the prescription dose level, where the isodose volumes increased with the RBE
LET
plans, e.g. up to 63% in the 3-beam plan for the smallest phantom target. Overall, the temporal lobes were better spared with the sagittal proton arc surrogate plans, e.g. a mean dose of 3.9 Gy compared to 6 Gy in the reference 3-beam plan (median value, RBE
1.1
).
Conclusion: Proton arc therapy has the potential to improve dose gradients to better spare cognitive brain structures. However, this is at the expense of increased low-dose/low-LET volumes, with possible implications for secondary cancer risks.
•An application for exploration and prediction of pelvic organ variability in radiotherapy.•Retrospective patient data are employed to predict anatomical changes in new incoming patients.•The ...prediction is linked to treatment plan evaluation, supporting the selection of the optimal treatment.•Usage scenarios and an evaluation; both conducted with eight domain experts.
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Radiotherapy (RT) requires meticulous planning prior to treatment, where the RT plan is optimized with organ delineations on a pre-treatment Computed Tomography (CT) scan of the patient. The conventionally fractionated treatment usually lasts several weeks. Random changes (e.g., rectal and bladder filling in prostate cancer patients) and systematic changes (e.g., weight loss) occur while the patient is being treated. Therefore, the delivered dose distribution may deviate from the planned. Modern technology, in particular image guidance, allows to minimize these deviations, but risks for the patient remain. We present PREVIS: a visual analytics tool for (i) the exploration and prediction of changes in patient anatomy during the upcoming treatment, and (ii) the assessment of treatment strategies, with respect to the anticipated changes. Records of during-treatment changes from a retrospective imaging cohort with complete data are employed in PREVIS, to infer expected anatomical changes of new incoming patients with incomplete data, using a generative model. Abstracted representations of the retrospective cohort partitioning provide insight into an underlying automated clustering, showing main modes of variation for past patients. Interactive similarity representations support an informed selection of matching between new incoming patients and past patients. A Principal Component Analysis (PCA)-based generative model describes the predicted spatial probability distributions of the incoming patient’s organs in the upcoming weeks of treatment, based on observations of past patients. The generative model is interactively linked to treatment plan evaluation, supporting the selection of the optimal treatment strategy. We present a usage scenario, demonstrating the applicability of PREVIS in a clinical research setting, and we evaluate our visual analytics tool with eight clinical researchers.
Most solid-state detectors, including 3D dosimeters, show lower signal in the Bragg peak than expected, a process termed quenching. The purpose of this study was to investigate how variation in ...chemical composition of a recently developed radiochromic, silicone-based 3D dosimeter influences the observed quenching in proton beams. The dependency of dose response on linear energy transfer, as calculated through Monte Carlo simulations of the dosimeter, was investigated in 60 MeV proton beams. We found that the amount of quenching varied with the chemical composition: peak-to-plateau ratios (1 cm into the plateau) ranged from 2.2 to 3.4, compared to 4.3 using an ionization chamber. The dose response, and thereby the quenching, was predominantly influenced by the curing agent concentration, which determined the dosimeter's deformation properties. The dose response was found to be linear at all depths. All chemical compositions of the dosimeter showed dose-rate dependency; however this was not dependent on the linear energy transfer. Track-structure theory was used to explain the observed quenching effects. In conclusion, this study shows that the silicone-based dosimeter has potential for use in measuring 3D-dose-distributions from proton beams.
The bladder is a tumour site well suited for adaptive radiotherapy (ART) due to large inter-fractional changes, but it also displays considerable intra-fractional motion. The aim of this study was to ...assess target coverage with a clinically applied method for plan selection ART and to estimate population-based and patient-specific intra-fractional margins, also relevant for a future re-optimisation strategy.
Nine patients treated in a clinical phase II ART trial of daily plan selection for bladder cancer were included. In the library plans, 5 mm isotropic margins were added to account for intra-fractional changes. Pre-treatment and weekly repeat magnetic resonance imaging (MRI) series were acquired in which a full three-dimensional (3D) volume was scanned every second min for 10 min (a total of 366 scans in 61 series). Initially, the bladder clinical target volume (CTV) was delineated in all scans. The t = 0 min scan was then rigidly registered to the planning computed tomography (CT) and plan selections were simulated using the CTV_0 (at t = 0 min). To assess intra-fractional motion, coverage of the CTV_10 (at t = 10 min) was quantified using the applied PTV. Population-based margins were calculated using the van Herk margin recipe while patient-specific margins were calculated using a linear model.
For 49% of the cases, the CTV_10 extended more than 5 mm outside the CTV_0. However, in 58 of the 61 cases (97%) CTV_10 was covered by the selected PTV. Population-based margins of 14 mm Sup/Ant, 9 mm Post and 5 mm Inf/Lat were sufficient to cover the bladder. Using patient-specific margins, the overlap between PTV and bowel-cavity was reduced from 137 cm(3) with the plan selection strategy to 24 cm(3).
In this phase II ART trial, 5 mm isotropic margin for intra-fractional motion was sufficient even though considerable intra-fractional motion was observed. In online re-optimised ART, population-based margin can be applied although patient-specific margins are preferable.
The aim of this study was to assess acute and late morbidity measured by the physician and patient-reported outcomes (PROs) in high-risk prostate cancer (PC) patients receiving whole pelvic ...intensity-modulated radiotherapy (IMRT) in the setting of a national clinical trial.
A total of 88 patients with adenocarcinoma of the prostate and high-risk parameters were enrolled from 2011 to 2013. All patients received 78 Gy in 39 fractions of IMRT delivering simultaneous 78 Gy to the prostate and 56 Gy to the seminal vesicles and lymph nodes. Physician-reported morbidity was assessed by CTCAE v.4.0. PROs were registered for gastro-intestinal (GI) by the RT-ARD score, genito-urinary (GU) by DAN-PSS, sexual and hormonal by EPIC-26, and quality of life (QoL) by EORTC QLQ-C30.
Median follow-up (FU) time was 4.6 years. No persistent late CTCAE grade 3+ morbidity was observed. Prevalence of CTCAE grade 2+ GI morbidities varied from 0 to 6% at baseline throughout FU time, except for diarrhea, which was reported in 19% of the patients post-RT. PROs revealed increased GI morbidity (≥1 monthly episode) for "rectal urgency", "use of pads", "incomplete evacuation", "mucus in stool" and "bowel function impact on QoL" all remained significantly different (p < .05) at 60 months compared to baseline. CTCAE grade 2+ GU and sexual morbidity were unchanged. GU PROs on obstructive and irritative GU items (≥daily episode) increased during RT and normalized at 24 months. No clinically significant differences were found in sexual, hormonal, and QoL scores compared to baseline.
Whole pelvic RT resulted in a mild to the moderate burden of late GI morbidities demonstrated by a relatively high prevalence of PROs. Whereas, physician-assessed morbidity revealed a low prevalence of late GI morbidity scores. This emphasizes the importance of using both PROs and physician-reported scoring scales when reporting late morbidity in clinical trials.
Stopping-power ratios (SPRs) are used in particle therapy to calculate particle range in patients. The heuristic CT-to-SPR conversion (Hounsfield Look-Up-Table, HLUT), needed for treatment planning, ...depends on CT-scan and reconstruction parameters as well as the specific HLUT definition. To assess inter-centre differences in these parameters, we performed a survey-based qualitative evaluation, as a first step towards better standardisation of CT-based SPR derivation.
A questionnaire was sent to twelve particle therapy centres (ten from Europe and two from USA). It asked for details on CT scanners, image acquisition and reconstruction, definition of the HLUT, body-region specific HLUT selection, investigations of beam-hardening and experimental validations of the HLUT. Technological improvements were rated regarding their potential to improve SPR accuracy.
Scan parameters and HLUT definition varied widely. Either the stoichiometric method (eight centres) or a tissue-substitute-only HLUT definition (three centres) was used. One centre combined both methods. The number of HLUT line segments varied widely between two and eleven. Nine centres had investigated influence of beam-hardening, often including patient-size dependence. Ten centres had validated their HLUT experimentally, with very different validation schemes. Most centres deemed dual-energy CT promising for improving SPR accuracy.
Large inter-centre variability was found in implementation of CT scans, image reconstruction and especially in specification of the CT-to-SPR conversion. A future standardisation would reduce time-intensive institution-specific efforts and variations in treatment quality. Due to the interdependency of multiple parameters, no conclusion can be drawn on the derived SPR accuracy and its inter-centre variability.
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