Corrigendum to "Two compound techniques for total body irradiation" [Tech. Innov. Patient Support Radiat. Oncol. 21 (2022) 1-7].

[This corrects the article DOI: 10.1016/j.tipsro.2021.11.006.].

Towards range-guidance in proton therapy to detect organ motion-induced dose degradations.

Introduction.Internal organ motion and deformations may cause dose degradations in proton therapy (PT) that are challenging to resolve using conventional image-guidance strategies. This study aimed to investigate the potential ofrange guidanceusing water-equivalent path length (WEPL) calculations to detect dose degradations occurring in PT.Materials and methods. Proton ranges were estimated using WEPL calculations. Field-specific isodose surfaces in the planning CT (pCT), from robustly optimised five-field proton plans (opposing lateral and three posterior/posterior oblique beams) for locally advanced prostate cancer patients, were used as starting points. WEPLs to each point on the field-specific isodoses in the pCT were calculated. The corresponding range for each point was found in the repeat CTs (rCTs). The spatial agreement between the resulting surfaces in the rCTs (hereafter referred to as iso-WEPLs) and the isodoses re-calculated in rCTs was evaluated for different dose levels and Hausdorff thresholds (2-5 mm). Finally, the sensitivity and specificity of detecting target dose degradation (V95% < 95%) using spatial agreement measures between the iso-WEPLs and isodoses in the pCT was evaluated.Results. The spatial agreement between the iso-WEPLs and isodoses in the rCTs depended on the Hausdorff threshold. The agreement was 65%-88% for a 2 mm threshold, 83%-96% for 3 mm, 90%-99% for 4 mm, and 94%-99% for 5 mm, across all fields and isodose levels. Minor differences were observed between the different isodose levels investigated. Target dose degradations were detected with 82%-100% sensitivity and 75%-80% specificity using a 2 mm Hausdorff threshold for the lateral fields.Conclusion. Iso-WEPLs were comparable to isodoses re-calculated in the rCTs. The proposed strategy could detect target dose degradations occurring in the rCTs and could be an alternative to a fully-fledged dose re-calculation to detect anatomical variations severely influencing the proton range.

Two compound techniques for total body irradiation.

INTRODUCTION: Total body irradiation (TBI) is an important treatment modality that is used in combination with chemotherapy in many stem cell transplantation protocols. Therefore, the quality of the irradiation is important. Two techniques for planning and delivering TBI are presented and compared. METHODS AND MATERIALS: The technique named ExIMRT is a combination of manually shaped conventional fields from an extended SSD and isocentric IMRT fields. The technique named ExVMAT is a combination of conventional and IMRT fields from an extended SSD and isocentric VMAT fields. Dosimetric data from 32 patients who were planned and treated according to one of the two techniques were compared. RESULTS: When comparing the two techniques, it is determined that the ExVMAT technique is able to significantly reduce the mean total volume overdosed by 120% from 408 to 12 cm3. The dose covering 98% of the total lung volume is significantly increased by this technique from a mean of 9.7 Gy to 10.3 Gy. Additionally, the dose covering 2% of the total kidney volume is significantly decreased from a mean of 12.8 to 12.5 Gy. Furthermore, the population-based variance of the median dose to the total lung volume, the heart and the volume of the body prescribed to 12.5 Gy is significantly reduced. The results are obtained without compromising overall treatment quality as treatment time or dose rate to the lungs. CONCLUSION: Using the ExVMAT technique, a superior dose distribution can be delivered both from a patient and a population perspective compared to the ExIMRT technique.

Dose response of three-dimensional silicone-based radiochromic dosimeters for photon irradiation in the presence of a magnetic field.

The magnetic field in magnetic resonance imaging guided radiotherapy (MRgRT) delivery systems influences charged-particle trajectories and hence the three-dimensional (3D) radiation dose distributions. This study investigated the dose-response as well as dose-rate and fractionation dependencies of silicone-based 3D radiochromic dosimeters for photon irradiation in a magnetic field using a 0.35 T MRgRT system. We found a linear dose response up to 22.6 Gy and no significant dose-rate dependency as a function of depth. A difference in optical response was observed for dosimeters irradiated in a single compared to multiple fractions. The dosimeter showed clinical potential for verification of MRgRT delivery.

Dose-response of deformable radiochromic dosimeters for spot scanning proton therapy.

Intrafractional motion and deformation influence proton therapy delivery for tumours in the thorax, abdomen and pelvis. This study aimed to test the dose-response of a compressively strained three-dimensional silicone-based radiochromic dosimeter during proton beam delivery. The dosimeter was read-out in its relaxed state using optical computed tomography and calibrated for the linear energy transfer, based on Monte Carlo simulations. A three-dimensional gamma analysis showed a 99.3% pass rate for 3%/3 mm and 93.9% for 2%/2 mm, for five superimposed measurements using deformation-including Monte Carlo dose calculations as reference. We conclude that the dosimeter's dose-response is unaffected by deformations.

Pelvic insufficiency fractures, dose volume parameters and plan optimization after radiotherapy for rectal cancer.

Pelvic insufficiency fractures (PIF) is a known but under-acknowledged late effect of pelvic radiotherapy. In rectal cancer, studies describing incidence of PIF and relation to dose volume relationships are lacking. The aim of this study was (i) to analyse dose volume histograms (DVH) from pelvic bones in patients with and without PIF, and (ii) to determine bone sparing capacity of 2 and 3 arc volumetric arc therapy (VMAT), intensity modulated radiotherapy (IMRT) and proton beam therapy (PBT), in rectal cancer patients treated with chemoradiotherapy (CRT). MATERIAL AND METHODS: Patients treated with CRT for primary rectal cancer underwent a 3-year pelvic MRI for identification of PIFs. Bone structures were retrospectively delineated, and DVHs were re-calculated. Comparative planning was done with 2 (original) and 3 arc VMAT, fixed field IMRT and PBT plans. RESULTS: 27 patients (18 men, mean age 64 years) were included and PIFs were identified in 9 (33%), most (n = 6) had multiple fracture sites. In general, patients with PIFs received higher doses to pelvic bones, and V30 Gy to the sacroiliac joint was non-significantly higher in patients with PIF 68.5% (60.1-69.3 IQR) vs. 56% (54.1-66.6 IQR), p = 0.064. Comparative planning showed that especially 3 arc VMAT and proton beam therapy could be optimized for bone. CONCLUSIONS: Patients, treated with VMAT based CRT for rectal cancer, have high rates of PIFs after 3 years. Patients with PIFs tended to have received higher doses to sacroiliac joints. Comparative planning demonstrated most pronounced bone sparing capacity of 3 arc VMAT and with PBT having the potential to further lower doses. These results should be validated in larger and preferably prospective cohorts.

Towards proton arc therapy: physical and biologically equivalent doses with increasing number of beams in pediatric brain irradiation.

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: RBE1.1; and RBELET, 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 RBELET 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, RBE1.1). 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.

Radiation doses to brain substructures associated with cognition in radiotherapy of pediatric brain tumors.

Background: Several brain substructures associated with cognition (BSCs) are located close to typical pediatric brain tumors. Pediatric patients therefore have considerable risks of neurocognitive impairment after brain radiotherapy. In this study, we investigated the radiation doses received by BSCs for three common locations of pediatric brain tumor entities. Material and methods: For ten patients in each group [posterior fossa ependymoma (PFE), craniopharyngioma (CP), and hemispheric ependymoma (HE)], the cumulative fraction of BSCs volumes receiving various dose levels were analyzed. We subsequently explored the differences in dose pattern between the three groups and used available dose response models from the literature to estimate treatment-induced intelligence quotient (IQ) decline. Results: Doses to BSCs were found to differ considerably between the groups, depending on their position relative to the tumor. Large inter-patient variations were observed in the ipsilateral structures of the HE groups, and at low doses for all three groups. IQ decline estimates differed depending on the model applied, presenting larger variations in the HE group. Conclusion: While there were notable differences in the dose patterns between the groups, the extent of estimated IQ decline depended more on the model applied. This inter-model variability should be considered in dose-effect assessments on cognitive outcomes of pediatric patients.

Robustness of elective lymph node target coverage with shrinking Planning Target Volume margins in external beam radiotherapy of locally advanced cervical cancer.

BACKGROUND AND PURPOSE: Image-Guidance decreases set-up uncertainties, which may allow for Planning Target Volume (PTV) margins reduction. This study evaluates the robustness of the elective lymph node target coverage to translational and rotational set-up errors in combination with shrinking PTV margins and determines the gain for the Organs At Risk (OARs). MATERIAL AND METHODS: Ten cervix cancer patients who underwent external beam radiotherapy with 45 Gy/25Fx were analysed. Daily Image-Guidance was based on bony registration of Cone Beam CT (CBCT) to planning CT (pCT) and daily couch correction (translation and yaw). On each pCT, four Volumetric Modulated Arc Therapy dose-plans were generated with PTV margins of 0, 3, 5 and 8 mm. The elective clinical target volume (CTV-E) was propagated from daily CBCTs to the pCT to evaluate daily CTV-E dose. Additional systematic translational isocenter shifts of 2 mm were simulated. D98% (dose received by 98% of the volume of interest) and D99.9% were extracted from each CTV-E for all dose-plans and scenarios. Total dose was accumulated by Dose-Volume Histogram addition. The dosimetric impact of PTV margin reduction on the OARs was evaluated through V30Gy (volume included within the 30 Gy isodose), V40Gy and body V43Gy. RESULTS: When decreasing the PTV margin from 5 to 0 mm, bowel V30Gy was decreased by 13% (from 247 cm3 to 214 cm3), body V43Gy by 19% (from 1462 cm3 to 1188 cm3) and PTV by 39% (from 1416 to 870 cm3). The dosimetric impact of combined systematic shifts and residual rotations on the elective target with a 0 mm PTV margin was a decrease of D98% (mean ±â€¯SD) from 44.1 Gy ±â€¯0.4 Gy to 43.7 Gy ±â€¯0.8 Gy and a minimum of 42.4 Gy. CONCLUSION: PTV margin reduction from 5 to 0 mm induced significant OARs dosimetric gains while elective target coverage remained robust to positioning uncertainties.

On-line dose-guidance to account for inter-fractional motion during proton therapy.

BACKGROUND AND PURPOSE: Proton therapy (PT) of extra-cranial tumour sites is challenged by density changes caused by inter-fractional organ motion. In this study we investigate on-line dose-guided PT (DGPT) to account inter-fractional target motion, exemplified by internal motion in the pelvis. MATERIALS AND METHODS: On-line DGPT involved re-calculating dose distributions with the isocenter shifted up to 15 mm from the position corresponding to conventional soft-tissue based image-guided PT (IGPT). The method was applied to patient models with simulated prostate/seminal vesicle target motion of ±3, ±5 and ±10 mm along the three cardinal axes. Treatment plans were created using either two lateral (gantry angles of 90°/270°) or two lateral oblique fields (gantry angles of 35°/325°). Target coverage and normal tissue doses from DGPT were compared to both soft-tissue and bony anatomy based IGPT. RESULTS: DGPT improved the dose distributions relative to soft-tissue based IGPT for 39 of 90 simulation scenarios using lateral fields and for 50 of 90 scenarios using lateral oblique fields. The greatest benefits of DGPT were seen for large motion, e.g. a median target coverage improvement of 13% was found for 10 mm anterior motion with lateral fields. DGPT also improved the dose distribution in comparison to bony anatomy IGPT in all cases. The best strategy was often to move the fields back towards the original target position prior to the simulated target motion. CONCLUSION: DGPT has the potential to better account for large inter-fractional organ motion in the pelvis than IGPT.

Validation of fast motion-including dose reconstruction for proton scanning therapy in the liver.

This study validates a method of fast motion-including dose reconstruction for proton pencil beam scanning in the liver. The method utilizes a commercial treatment planning system (TPS) and calculates the delivered dose for any translational 3D target motion. Data from ten liver patients previously treated with photon radiotherapy with intrafraction tumour motion monitoring were used. The dose reconstruction method utilises an in-house developed program to incorporate beam's-eye-view tumour motion by shifting each spot in the opposite direction of the tumour and in-depth motion as beam energy changes for each spot. The doses are then calculated on a single CT phase in the TPS. Two aspects of the dose reconstruction were assessed: (1) The accuracy of reconstruction, by comparing dose reconstructions created using 4DCT motion with ground truth doses obtained by calculating phase specific doses in all 4DCT phases and summing up these partial doses. (2) The error caused by assuming 4DCT motion, by comparing reconstructions with 4DCT motion and actual tumour motion. The CTV homogeneity index (HI) and the root-mean-square (rms) dose error for all dose points receiving >70%, >80% and >90% of the prescribed dose were calculated. The dose reconstruction resulted in mean (range) absolute CTV HI errors of 1.0% (0.0-3.0)% and rms dose errors of 2.5% (1.0%-5.3%), 2.1% (0.9%-4.5%), and 1.8% (0.7%-3.7%) for >70%, >80% and >90% doses, respectively, when compared with the ground truth. The assumption of 4DCT motion resulted in mean (range) absolute CTV HI errors of 5.9% (0.0-15.0)% and rms dose errors of 6.3% (3.9%-12.6%), 5.9% (3.4%-12.5%), and 5.4% (2.6%-12.1%) for >70%, >80% and >90% doses, respectively. The investigated method allows tumour dose reconstruction with the actual tumour motion and results in significantly smaller dose errors than those caused by assuming that motion at treatment is identical to the 4DCT motion.

Theoretical and experimental analysis of photon counting detector CT for proton stopping power prediction.

PURPOSE: Photon counting detectors (PCDs) are being introduced in advanced x-ray computed tomography (CT) scanners. From a single PCD-CT acquisition, multiple images can be reconstructed, each based on only a part of the original x-ray spectrum. In this study, we investigated whether PCD-CT can be used to estimate stopping power ratios (SPRs) for proton therapy treatment planning, both by comparing to other SPR methods proposed for single energy CT (SECT) and dual energy CT (DECT) as well as to experimental measurements. METHODS: A previously developed DECT-based SPR estimation method was adapted to PCD-CT data, by adjusting the estimation equations to allow for more energy spectra. The method was calibrated directly on noisy data to increase the robustness toward image noise. The new PCD SPR estimation method was tested in theoretical calculations as well as in an experimental setup, using both four and two energy bin PCD-CT images, and through comparison to two other SPR methods proposed for SECT and DECT. These two methods were also evaluated on PCD-CT images, full spectrum (one-bin) or two-bin images, respectively. In a theoretical framework, we evaluated the effect of patient-specific tissue variations (density and elemental composition) and image noise on the SPR accuracy; the latter effect was assessed by applying three different noise levels (low, medium, and high noise). SPR estimates derived using real PCD-CT images were compared to experimentally measured SPRs in nine organic tissue samples, including fat, muscle, and bone tissues. RESULTS: For the theoretical calculations, the root-mean-square error (RMSE) of the SPR estimation was 0.1% for the new PCD method using both two and four energy bins, compared to 0.2% and 0.7% for the DECT- and SECT-based method, respectively. The PCD method was found to be very robust toward CT image noise, with a RMSE of 2.7% when high noise was added to the CT numbers. Introducing tissue variations, the RMSE only increased to 0.5%; even when adding high image noise to the changed tissues, the RMSE stayed within 3.1%. In the experimental measurements, the RMSE over the nine tissue samples was 0.8% when using two energy bins, and 1.0% for the four-bin images. CONCLUSIONS: In all tested cases, the new PCD method produced similar or better results than the SECT- and DECT-based methods, showing an overall improvement of the SPR accuracy. This study thus demonstrated that PCD-CT scans will be a qualified candidate for SPR estimations.

Inter-centre variability of CT-based stopping-power prediction in particle therapy: Survey-based evaluation.

BACKGROUND AND PURPOSE: 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. MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

A biological modelling based comparison of radiotherapy plan robustness using photons vs protons for focal prostate boosting.

BACKGROUND AND PURPOSE: Focal tumour boosting is currently explored in radiotherapy of prostate cancer to increase tumour control. In this study we applied dose response models for both tumour control and normal tissue complications to explore the benefit of proton therapy (PT) combined with focal tumour boosting, also when accounting for inter-fractional motion. MATERIALS AND METHODS: CT scans of seven patients fused with MRI-based index volumes were used. Two volumetric modulated arc therapy (VMAT) plans were created for each patient; one with conventional dose (77 Gy) to the entire prostate, and one with an additional integrated boost (total dose of 95 Gy) to the index lesion. Two corresponding intensity modulated PT (IMPT) plans were created using two lateral opposing spot scanning beams. All plans were evaluated using an MRI-based tumour control probability (TCP) model and normal tissue complication probability (NTCP) models for the rectum and bladder. Plan robustness was evaluated using dose re-calculations on repeat cone-beam CTs. RESULTS: Across all plans, median TCP increased from 86% (range: 59-98%) without boost to 97% (range: 96-99%) with boost. IMPT plans had lower rectum NTCPs (e.g. 3% vs. 4% for boost plans) but higher bladder NTCPs (20% vs. 18% for boost plans), yet only the bladder NTCPs remained different in the cone beam CT-based re-calculations. CONCLUSIONS: Focal tumour boosting can be delivered with either VMAT or protons, and increases the predicted TCP. The small benefit of IMPT when assessing the planned dose distributions was lost when accounting for inter-fractional motion.

Consequences of introducing geometric GTV to CTV margin expansion in DAHANCA contouring guidelines for head and neck radiotherapy.

BACKGROUND AND PURPOSE: Defining margins around the Gross Tumour Volume (GTV) to create a Clinical Target Volume (CTV) for head and neck cancer radiotherapy has traditionally been based on presumed knowledge of anatomical routes of spread. However, using a concentric geometric expansion around the GTV may be more reproducible. The purpose of this study was to analyse the inter-observer consistency of geometric CTV delineation with adaptation for anatomical boundaries versus anatomically defined CTVs. MATERIAL AND METHODS: Radiation oncologists at four Danish cancer centres delineated high, intermediate and elective dose CTVs (CTV1, CTV2 and CTV3, respectively) in a patient-case template (stage IV squamous cell carcinoma of the oropharynx), first using mainly anatomical margins (original standard) and then using concentric geometric expansion (new standard). Each centre made a dummy-run radiotherapy plan based on the delineated CTVs. The difference between the CTV contours and the radiotherapy plans was evaluated across the centres. RESULTS: Anatomy-based contours were significantly more heterogenous and showed larger volume differences between centres than geometric margins. Dice similarity coefficient increased by 0.29 and mean surface distance decreased by 4mm for CTV1. Use of consistent CTV volumes resulted in more consistent irradiated volumes between centres. CONCLUSION: Introduction of geometric margins resulted in more uniform CTV1 and CTV2 delineation. Geometric CTV expansion was easier, left less room for misinterpretation, and resulted in more uniform treatment plans with similar irradiated high and intermediate dose volumes across all centres.

Local recurrences after curative IMRT for HNSCC: Effect of different GTV to high-dose CTV margins.

INTRODUCTION: The aim was to analyze position of CT-verified local recurrences (LR) and local control (LC) among three centers that used different GTV to CTV1 margins. MATERIALS AND METHODS: In total, 1576 patients completing radical primary IMRT for larynx, pharynx, oral cavity HNSCC in three centers in Denmark between 2006 and 2012 were included. CT-verified LRs were analyzed as possible points of recurrence origin and compared between groups of small (0-2.5 mm), larger (>2.5 mm), and anatomical GTV-CTV1 margins. The recurrence point's position relative to the GTV and 95% prescription dose was evaluated. Overall local control rate was evaluated using Cox uni- and multi-variate analysis. RESULTS: After a median follow-up of 41 months, 272 patients had local failure. Median GTV-CTV1 margin in Center1, 2 and 3 was 0.0, 3.7 and 9.7 mm, respectively. 51% of local recurrences were inside the GTV. No difference in distribution of LRs in relation to GTV surface (p = 0.4) or the dose to LRs (p = 0.2) was detected between the groups. A difference in LC was found univariate between the centers (p = 0.03), but not in multivariate analysis (p = 0.4). CONCLUSIONS: No relation was found between the recurrences' distributions as function of the margins used at three centers. In multivariate analysis, local control was not influenced by the centers.

Validation of proton stopping power ratio estimation based on dual energy CT using fresh tissue samples.

Dual energy CT (DECT) has been shown, in theoretical and phantom studies, to improve the stopping power ratio (SPR) determination used for proton treatment planning compared to the use of single energy CT (SECT). However, it has not been shown that this also extends to organic tissues. The purpose of this study was therefore to investigate the accuracy of SPR estimation for fresh pork and beef tissue samples used as surrogates of human tissues. The reference SPRs for fourteen tissue samples, which included fat, muscle and femur bone, were measured using proton pencil beams. The tissue samples were subsequently CT scanned using four different scanners with different dual energy acquisition modes, giving in total six DECT-based SPR estimations for each sample. The SPR was estimated using a proprietary algorithm (syngo.via DE Rho/Z Maps, Siemens Healthcare, Forchheim, Germany) for extracting the electron density and the effective atomic number. SECT images were also acquired and SECT-based SPR estimations were performed using a clinical Hounsfield look-up table. The mean and standard deviation of the SPR over large volume-of-interests were calculated. For the six different DECT acquisition methods, the root-mean-square errors (RMSEs) for the SPR estimates over all tissue samples were between 0.9% and 1.5%. For the SECT-based SPR estimation the RMSE was 2.8%. For one DECT acquisition method, a positive bias was seen in the SPR estimates, having a mean error of 1.3%. The largest errors were found in the very dense cortical bone from a beef femur. This study confirms the advantages of DECT-based SPR estimation although good results were also obtained using SECT for most tissues.

Biological dose and complication probabilities for the rectum and bladder based on linear energy transfer distributions in spot scanning proton therapy of prostate cancer.

BACKGROUND: 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 (LETd) distributions for spot scanning PT of prostate cancer patients using different beam angle configurations. In addition, we derived RBE-weighted (RBEw) dose distributions and related normal tissue complication probabilities (NTCPs) for the rectum and bladder. MATERIAL AND METHODS: A total of 21 spot scanning proton plans were created for each of six patients using a prescription dose of 78 Gy(RBE1.1), with each plan using two 'mirrored' beams with gantry angles from 110°/250° to 70°/290°, in steps of 2°. Physical dose and LETd distributions were calculated as well as RBEw 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. RESULTS: For anterior oblique (AO) configurations, the rectum LETd volume and RBEw dose increased with increasing angles off the lateral opposing axis, with the RBEw 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 D1cm3 constraint was fulfilled for most patients/configurations when using uniform RBE but not for any patient/configuration with variable RBE models. CONCLUSIONS: 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.

Evaluating the influence of organ motion during photon vs. proton therapy for locally advanced prostate cancer using biological models.

BACKGROUND: Proton therapy (PT) may have a normal tissue sparing potential when co-irradiating pelvic lymph nodes in patients with locally advanced prostate cancer, but may also be more sensitive towards organ motion in the pelvis. Building upon a previous study identifying motion-robust proton beam angles for pelvic irradiation, we aimed to evaluate the influence of organ motion for PT using biological models, and to compare this with contemporary photon-based RT. MATERIAL AND METHODS: Eight locally advanced prostate cancer patients with a planning CT (pCT) and 8-9 repeated CT scans (rCTs) were included. Two PT plans were created, one using two lateral opposed beams at gantry angles of 90°/270° and the other using two lateral oblique beams at 35°/325°; these were compared with volumetric modulated arc therapy (VMAT) plans. All plans were optimised on the pCT and subsequently re-calculated on each rCT (following rigid alignment on the prostate). Dose distributions in organs at risk (OARs) were evaluated using mean dose, generalized equivalent uniform doses (gEUDs) and normal tissue complication probabilities (NTCPs), while mean dose and the volume receiving 98% of the dose (V98%) were used for the targets. RESULTS: PT significantly reduced the mean dose to the OARs and a correlation was seen in the pCTs between the prostate PTV overlapping the relevant OAR and OAR NTCPs, as was also the case for the VMAT plans. The best prostate target coverage across the rCTs for the IMPT plans were seen with two lateral opposed beams, although a poor coverage of the lymph node target was apparent based on V98% compared to the VMAT plans. CONCLUSIONS: PT reduced the mean dose to normal tissues in the irradiation of pelvic lymph nodes and a strong association between the volume overlap and NTCPs in the pCTs were found.