Proton Radiotherapy Plans Research Articles

Evolution of Proton Radiation Therapy Brainstem Constraints on the Pediatric Proton/Photon Consortium Registry

Increasing concern that brainstem toxicity incidence after proton radiation therapy might be higher than with photons led to a 2014 University of Florida (UF) landmark paper identifying its risk factors and proposing more conservative dose constraints. We evaluated how practice patterns changed among the Pediatric Proton/Photon Consortium Registry (PPCR). This prospective multicenter cohort study gathered data from patients under the age of 22 years enrolled on the PPCR, treated between 2002 and 2019 for primary posterior fossa brain tumors. After standardizing brainstem contours, we garnered dosimetry data and correlated those meeting the 2014 proton-specific brainstem constraint guidelines by treatment era, histology, and extent of surgical resection. A total of 467 patients with evaluable proton radiation therapy plans were reviewed. Median age was 7.1 years (range: <1-21.9), 63.0% (n = 296) were men, 76.0% (n = 357) were White, and predominant histology was medulloblastoma (55.0%, n = 256), followed by ependymoma (27.0%, n = 125). Extent of resection was mainly gross total resection (GTR) (67.0%, n = 312), followed by subtotal resection (STR) or biopsy (20.0%, n = 92), and near total resection (NTR) (9.2%, n = 43). The UF brainstem constraint metrics most often exceeded were the goal D50% of 52.4 gray relative biological equivalents (43.3%, n = 202) and maximal D50% of 54 gray relative biological equivalents (12.6%, n = 59). The compliance rate increased after the new guidelines (2002-2014: 64.0% vs 2015-2019: 74.6%, P = .02), except for ependymoma (46.3% pre- vs 50.0% post-guidelines, P = .86), presenting lower compliance (48.8%) in comparison to medulloblastoma/ primitive neuroectodermal tumors/pineoblastoma (77.7%), glioma (89.1%), and atypical teratoid/rhabdoid tumors (90.9%) (P < .001). Degree of surgical resection did not affect compliance rates (GTR/NTR 71.0% vs STR/biopsy 72.8%, P = .45), even within the ependymoma subset (GTR/NTR 50.5% vs STR/biopsy 38.1%, P = .82). Since the publication of the UF guidelines, the pediatric proton community has implemented more conservative brainstem constraints in all patients except those with ependymoma, irrespective of residual disease after surgery. Future work will evaluate if this change in practice is associated with decreased rates of brainstem toxicity.

Dose-Painting Proton Radiotherapy Guided by Functional MRI in Non-enhancing High-Grade Gliomas

AimsThis study aimed to demonstrate the feasibility and evaluate the dosimetric effect and clinical impact of dose-painting proton radiotherapy (PRT) guided by functional MRI in non-enhancing high-grade gliomas (NE-HGGs). Materials and methodsThe 3D-ASL and T2 FLAIR MR images of ten patients with NE-HGGs before radiotherapy were studied retrospectively. The hyperintensity on T2 FLAIR was used to generate the planning target volume (PTV), and the high-perfusion volume on 3D-ASL (PTV-ASL) was used to generate the simultaneous integrated boost (SIB) volume. Each patient received pencil beam scanning PRT and photon intensity-modulated radiotherapy (IMRT). There were five plans in each modality: (1) Uniform plans (IMRT60 vs. PRT60): 60Gy in 30 fractions to the PTV. (2)–(5) SIB plans (IMRT72, 84, 96, 108 vs. PRT72, 84, 96, 108): Uniform plan plus additional dose boost to PTV-ASL in 30 fractions to 72, 84, 96, 108 Gy. The dosimetric differences between various plans were compared. The clinical effects of target volume and organs at risk (OARs) were assessed using biological models for both tumor control probability (TCP) and normal tissue complication probability (NTCP). ResultsCompared with the IMRT plan, the D2 and D50 of the PRT plans with the same prescription dose increased by 1.27–4.12% and 0.64–2.01%, respectively; the R30 decreased by > 32%; the dose of brainstem and chiasma decreased by > 27% and >32%; and the dose of normal brain tissue (Br-PTV), optic nerves, eyeballs, lens, cochlea, spinal cord, and hippocampus decreased by > 50% (P < 0.05). The maximum necessary dose was 96GyE to achieve >98% TCP for PRT, and it was 84Gy to achieve >91% TCP for IMRT. The average NTCP of Br-PTV was 1.30% and 1.90% for PRT and IMRT at the maximum dose escalation, respectively. The NTCP values of the remaining OARs approached zero in all PRT plans. ConclusionThe functional MRI-guided dose escalation using PRT is feasible while sparing the OARs constraints and demonstrates a potential clinical benefit by improving TCP with no or minimal increase in NCTP for tissues outside the PTV. This retrospective study suggested that the use of PRT-based SIB guided by functional MRI may represent a strategy to provide benefits for patients with NE-HGGs.

Proton Therapy for Advanced Juvenile Nasopharyngeal Angiofibroma.

To provide the first report on proton radiotherapy (PRT) in the management of advanced nasopharyngeal angiofibroma (JNA) and evaluate potential benefits compared to conformal photon therapy (XRT). We retrospectively reviewed 10 consecutive patients undergoing PRT for advanced JNA in a definitive or postoperative setting with a relative biological effectiveness weighted dose of 45 Gy in 25 fractions between 2012 and 2022 at the Heidelberg Ion Beam Therapy Center. Furthermore, dosimetric comparisons and risk estimations for short- and long-term radiation-induced complications between PRT plans and helical XRT plans were conducted. PRT was well tolerated, with only low-grade acute toxicities (CTCAE I-II) being reported. The local control rate was 100% after a median follow-up of 27.0 (interquartile range 13.3-58.0) months. PRT resulted in considerable tumor shrinkage, leading to complete remission in five patients and bearing the potential to provide partial or complete symptom relief. Favorable dosimetric outcomes in critical brain substructures by the use of PRT translated into reduced estimated risks for neurocognitive impairment and radiation-induced CNS malignancies compared to XRT. PRT is an effective treatment option for advanced JNA with minimal acute morbidity and the potential for reduced radiation-induced long-term complications.

Assessment of dose perturbations for metal stent in photon and proton radiotherapy plans for hepatocellular carcinoma

BackgroundThe present study aimed to investigate the dosimetric impact of metal stent for photon and proton treatment plans in hepatocellular carcinoma.MethodsWith computed tomography data of a water-equivalent solid phantom, dose perturbation caused by a metal stent included in the photon and proton treatment of hepatocellular carcinoma was evaluated by comparing Eclipse and RayStation treatment planning system (TPS) to a Monte Carlo (MC) based dose calculator. Photon and proton plans were created with anterior–posterior/posterior-anterior (AP/PA) fields using a 6 MV beam and AP/PA fields of a wobbling beam using 150 MeV and a 10 cm ridge filter. The difference in dose distributions and dosimetric parameters were compared depending on the stent's positions (the bile duct (GB) and intestinal tract (GI)) and angles (0°, 45°, and 90°). Additionally, the dose variation in the target volume including the stent was comparatively evaluated through dose volume histogram (DVH) analysis. And the comparison of clinical cases was carried out in the same way.ResultsPercentage differences in the dosimetric parameters calculated by MC ranged from − 7.0 to 3.9% for the photon plan and − 33.7 to 4.3% for the proton plan, depending on the angle at which the GB and GI stents were placed, compared to those without the stent. The maximum difference was observed at the minimum dose (Dmin), which was observed in both photon and proton plans in the GB and GI stents deployed at a 90° incidence angle. The parameter differences were greater in the proton plan than in photon plan. The target volume showed various dose variations depending on positions and angles of stent for both beams. Compared with no-stent, the doses within the target volume containing the GI and GB stents for the photon beam were overestimated in the high-dose area at 0°, nearly equal within 1% at 45°, and underestimated at 90°. These doses to the proton beam were underestimated at all angles, and the amount of underdose to the target volume increased with an increase in the stent angle. However, the difference was significantly greater with the proton plan than the photon plan.ConclusionsDose perturbations within the target volume due to the presence of the metal stent were not observed in the TPS calculations for photon and proton beams, but MC was used to confirm that there are dose variations within the target volume. The MC results found that delivery of the treatment beam avoiding the stent was the best method to prevent target volume underdose.

Post-Mastectomy Acute Skin Toxicity Assessment Between Particle and Photon Therapy

<h3>Purpose/Objective(s)</h3> To compare acute skin toxicity following post-mastectomy photon (XRT) and skin-sparing proton radiotherapy (PRT). <h3>Materials/Methods</h3> 179 consecutive women with unilateral, non-inflammatory breast cancer were treated with conventionally fractionated post-mastectomy radiotherapy (PMRT) between 2015 and 2019. Prescription was 50 Gy (RBE) in 25 fractions to the chest wall and regional lymph nodes. PRT was administered with a median of two multi-field optimized fields (intensity modulated proton therapy). The chest wall skin was defined as the first 3 mm from the external body surface. XRT and PRT planning objectives with respect to skin were to achieve microscopic disease target coverage while limiting surface hot spots. For XRT 3-5 mm daily bolus was most commonly employed to achieve these objectives. PRT planning objectives were V90% > 90% and D1cc < 102%. Dermatitis was evaluated by physicians using CTCAE version 4.0, and patient reported outcomes (PROs) regarding skin burn severity were prospectively collected. <h3>Results</h3> Treatment was PRT in 96 and XRT in 83 (95% 3D conformal radiotherapy with a wide tangent technique, 5% intensity modulated radiotherapy). There was no significant difference between the two groups with respect to age, stage, receipt of chemotherapy, immediate breast reconstruction, diabetes mellitus, body mass index (BMI), or current or former smoking history. 65% PRT and 61% XRT pts had immediate breast reconstruction. Median follow-up was 25 months. There was no significant difference in grade ≥2 or grade 3 dermatitis between PRT and XRT at 47% vs 48%, <i>P</i> = 0.86 and 3% vs 7%, <i>P</i> = 0.22, respectively. There was a trend for higher grade ≥2 dermatitis in current or former smokers vs never smokers (60% vs 43%, <i>P</i> = 0.06). BMI (<i>P</i> = 0.11), diabetes (<i>P</i> = 0.41), and breast reconstruction (<i>P</i> = 0.63) were also not associated with grade ≥2 dermatitis. Dosimetric parameters including the skin dose to 1 cc (<i>P</i> < 0.0001) and 10 cc (<i>P</i> < 0.0001), skin V105% (<i>P</i> < 0.0001), and the mean skin dose (<i>P</i> = 0.0009) were significantly associated with grade ≥2 dermatitis. In multivariable analysis, former or current tobacco use was the only variable significantly associated grade ≥2 dermatitis (OR 2.02 [1.01-4.06], <i>P</i> = 0.05). Silver sulfadiazine was prescribed in 30% of PRT and 42% of XRT pts (<i>P</i> = 0.1). There was no difference in moderate or more severe patient-reported skin burns between PRT and XRT (40% vs 40%, <i>P</i> = 1.0). <h3>Conclusion</h3> Post-mastectomy PRT administered with our skin-sparing technique is not associated with higher rates of acute dermatitis than XRT.

Reducing motion artifact in sequential-scan dual-energy CT imaging by incorporating deformable registration within joint statistical image reconstruction

Dual-energy computed tomography (DECT) has been widely used to reconstruct basis components. In previous studies, ou DECT algorithm has shown high accuracy in stopping power ratio (SPR) estimation of fixed objects for proton radiotherapy planning. However, patient movement between sequential data acquisitions may lead to severe motion artifacts in the component images. In order to reduce or eliminate the motion artifacts in clinical applications, we combine a deformable registration method with an accurate joint statistical iterative reconstruction algorithm, dual-energy alternating minimization (DEAM). Image registration is a process of geometrically aligning two or more images. We implement a multi-modality symmetric deformable registration method based on Advanced Normalization Tools (ANTs) to automatically align the scans we acquire for the same patient. The precalculated registration mapping and its inverse are then embedded into each iteration of the DEAM algorithm. The performance of warped DEAM is quantitatively assessed. Theoretically, the performance of warped DEAM on moved patients should be comparable to the performance of the original DEAM algorithm on fixed objects. The warped DEAM algorithm reduces motion artifacts while preserving the accuracy of the iterative joint statistical CT reconstruction algorithm, which enables us to reconstruct accurate results from sequentially scanned dual-energy patient data.

The Evolution of Proton Brainstem Constraints: A Multi-Institutional Study from the Pediatric Proton/Photon Consortium Registry (PPCR)

A landmark paper (Indelicato, Acta Onc, 2014) evaluating brainstem (BS) injury in pediatric patients treated with proton radiotherapy (PRT) was published at the end of 2014. Here we evaluate how practice patterns changed in patients with primary posterior fossa brain tumors enrolled on the multi-institutional Pediatric Proton/Photon Consortium Registry (PPCR). Clinical data was obtained from 15 PPCR institutions on patients <22 years-old treated for primary brain tumors of the posterior fossa. Commercially available software was used to evaluate, standardize BS contours, and garner dosimetry data (BS D50%, D10%, Dmax(0.1cc), reported in GyRBE. Plans consistent with the 2014 Indelicato et al. guidelines (BS goal – maximal constraint: Dmax 56.6 – 58 GyRBE, D10% 55.4 – 56 GyRBE, D50% 52.4 – 54 GyRBE) were labeled as treatment concordant (TC), while all others were considered deviating (TD) from the proposed guidelines. The rates of TC were compared by era (pre vs. post guidelines), histology (any), and degree of surgical resection (any histology and ependymoma only) employing Fisher’s exact test and Benjamini-Hochberg correction. 451 patients with evaluable PRT plans of the 502 PPCR-enrolled patients with posterior fossa tumors treated from 2004-2019 were reviewed. Median age was 7 years (range: 1 – 21), 62% were male, and 55% were white. Histology was medulloblastoma (56%), ependymoma (26%), glioma (10%), and ATRT (4%). Extent of resection was GTR (66%), NTR (9%), STR/biopsy (20%), and no surgery (3%), with 2% not reported. 66% were treated with chemotherapy, and 4% had prior radiotherapy. The BS constraints most often exceeded were the goal D50% of 52.4 GyRBE (28% of plans) and maximal D50% of 54 GyRBE (13% of plans). The TC rate increased after the new guidelines (2015-2019: 76% vs. 2004-2014: 65%, p = 0.009), except the ependymoma subset TC rate (49% pre vs. 51% post guidelines, p = 0.4) with no increasing trend. The TC rate was less for ependymoma (50%) in comparison to medulloblastoma (76%), glioma (89%), and ATRT (95%) (p < 0.001 for each comparison). Degree of surgical resection did not affect TC rates in the entire cohort (GTR/NTR 70.9% vs. STR/biopsy 73.9%, p = 0.34) or the subset with ependymoma (GTR/NTR 50.5% vs. STR/biopsy 42.1%, p = 0.34). The pediatric proton community has adopted more conservative brainstem constraints over time, yet children with ependymoma are less likely to have these constraints met irrespective of residual disease after surgery. Future work will evaluate if this change in practice is associated with decreased rates of brainstem injury in the PPCR cohort.

In silico comparison of the dosimetric impacts of a greater omentum spacer for abdominal and pelvic tumors in carbon-ion, proton and photon radiotherapy

PurposeThe purpose of this study was to compare carbon-ion (C-ion), proton and photon radiotherapy (RT) plans with regard to dose reduction of the gastrointestinal (GI) tract by using a greater omentum spacer (GO spacer).MethodsWe retrospectively retrieved data for ten patients who received the GO spacer as surgical spacer placement for abdominal and pelvic tumors. Simulation plans were created on pre-spacer Computed Tomography (CT) and post-spacer CT for C-ion RT, proton RT and photon RT to compare the dose of the GI tract. The plans were normalized so that at least 95% of the planning target volume (PTV) received 70 Gy (relative biological effectiveness equivalent) delivered in 35 fractions. All plans were created with the lowest possible dose to the GI tract under conditions that meet the dose constraints for the PTV and spinal cord (maximum dose < 45 Gy). The part of the GI tract to be evaluated was defined as that most adjacent to the PTV. C-ion RT plans and proton RT plans were calculated by a spot scanning technique, and photon RT plans were calculated employing by fixed-field intensity-modulated radiation therapy.ResultsD2 cc and V10–70 of the GI tract were significantly lower on post-spacer plans than on pre-spacer plans for all three RT modalities. Regarding post-spacer plans, D2 cc of the GI tract was significantly lower on C-ion RT plans and proton RT plans than on photon RT plans (C-ion vs photon p = 0.001, proton vs photon p = 0.002). However, there was no significant difference between C-ion RT plans and proton RT plans for D2 cc of the GI tract (C-ion vs proton p = 0.992). In the photon RT plan for one patient, D2 cc of the GI tract did not meet < 50 Gy.ConclusionsThe GO spacer shows a significant dose reduction effect on the GI tract.

EP-1720 Evaluation of dose perturbations for metal stent in photon and proton radiotherapy planning

EP-1720 Evaluation of dose perturbations for metal stent in photon and proton radiotherapy planning

LET-weighted doses effectively reduce biological variability in proton radiotherapy planning

Variations in proton relative biological effectiveness (RBE) with linear energy transfer (LET) remain one of the largest sources of uncertainty in proton radiotherapy. This work seeks to identify metrics which can be applied to mitigate these effects in treatment optimisation, and quantify their effectiveness. Three different metrics—dose, dose × LET and an LET-weighted dose defined as where is the dose-averaged LET—were compared with in vitro experimental studies of proton RBE and clinical treatment plans incorporating RBE models. In each system the biological effects of protons were plotted against these metrics to quantify the degree of variation introduced by unaccounted-for RBE uncertainties. As expected, the LET-dependence of RBE introduces significant variability in the biological effects of protons when plotted against dose alone. Plotting biological effects against dose × LET significantly over-estimated the impact of LET on cell survival, and typically produced even larger spreads in biological effect. LET-weighted dose was shown to have superior correlation to biological effect in both experimental data and clinical plans. For prostate and medulloblastoma treatment plans, the average RBE-associated variability in biological effect is ±5% of the prescribed dose, but is reduced to less than 1% using LET-weighting. While not a replacement for full RBE models, simplified metrics such as this LET-weighted dose can be used to account for the majority of variability which arises from the LET-dependence of RBE with reduced need for biological parameterisation. These metrics may be used to identify regions in normal tissues which may see unexpectedly high effects due to end-of-range elevations of RBE, or as part of a more general tool for biological optimisation in proton therapy.

RONC-11. EVALUATION OF DIFFERENT RADIOTHERAPY TECHNIQUES ON INCIDENTAL RADIATION DOSES TO THE WHOLE VENTRICULAR SYSTEM DURING FOCAL IRRADIATION FOR NON GERMINOMATOUS GERM CELL TUMOURS AFTER CHEMOTHERAPY

In Europe, patients with localized nongerminomatous germ cell tumours (NGGCT) are treated with focal radiotherapy. It is not sure whether this approach leads to excess periventricular recurrences in patients with a germinomatous component in the tumour. Data suggest that a dose of 20 Gy may be sufficient to control microscopic geminomatous disease. We evaluated the dose received to the whole ventricular system (WVS) using different techniques when delivering 54 Gy to the tumourbed. MATERIALS AND The WVS was delineated on the treatment planning CT of five patients diagnosed with NGGCT (2 pineal, 2 suprasellar and one bifocal). All patients had received proton radiotherapy following chemotherapy. We generated five photon plans: two coplanar, one noncoplanar and one tomotherapy plan. For the purpose of comparison the original proton radiotherapy plans were slightly modified. Mean WVS dose and the WVS volume receiving 20 Gy (V20) were analysed. Mean WVS dose with photons was 37 Gy [range 27-47] (coplanar: 35 Gy [27-41], noncoplanar: 38 Gy [33-43], tomotherapy: 40 Gy [34-47]) and with protons 35 Gy [28-42]. The WVS V20 was 78 % [range 58-90] with photons (coplanar: 73% [56-90], noncoplanar: 81% [73-90], tomotherapy: 88% [71-100]) and 68 % [55-80] with protons. The unintentional WVS dose varies between the different treatment techniques. Careful pattern of failure studies correlated with radiation dosimetry and clinical-pathological features are needed to define the role of WVS irradiation in NGGCTS.

Intensity-modulated radiotherapy for whole pelvis irradiation in prostate cancer: A dosimetric and plan robustness study between photons and protons.

To evaluate the dosimetric impact and plan robustness of using Pencil Beam Scanning (PBS) in patients that requires prophylactic pelvic lymph nodes (PLNs) irradiation for prostate cancer. Five intermediate to high-risk prostate patients previously treated using volumetric modulated arc therapy (VMAT), were selected for this study. Comparative proton radiotherapy plans were generated, where a three-field intensity modulated proton therapy (IMPT) plan was for the phase 1 planning target volume (PTV1) with PLNs. A technique with two posterior oblique fields using single field uniform dose (SFUD) was used for phase 2 (PTV2) volume, that comprises of the prostate and proximal seminal vesicles (Pro + proxSVs). Plan evaluation was performed on PTV coverage and dose to the organs at risk (OARs) using VMAT plans as a baseline (BL). Robust analysis on clinical target volume (CTV) coverage for the PBS plans was simulated with a 3 and 5 mm setup errors and a 3.5% range uncertainty. For target coverage, PTV1 and PTV2 showed negligible differences with a comparable homogeneity index (HI) values for both modalities. Proton plans produced a statistically significant lower mean dose to the bladder (32.5 Gy(RBE) vs. 46.5 Gy) and rectum (33.6 Gy(RBE) vs. 42.7 Gy). Dose to the bladder and rectum was equivalent at the high dose region. For the bowel cavity, the mean dose for proton plans were 45% lower compared to VMAT plans. Similarly, proton plans were able to achieve an overall reduction in integral dose for both treatment phase. CTV coverage remained high with all the simulated setup and range errors. Proposed beam geometries for PTV1 and PTV2 proton plans presented good treatment accuracy with similar target coverage as the VMAT plans. Better sparing of OARs was achieved at the low-medium dose region for the proton plans.

Left hippocampal dosimetry correlates with visual and verbal memory outcomes in survivors of pediatric brain tumors.

Radiotherapy (RT) in the pediatric brain tumor population causes late neurocognitive effects. In the current study, the authors investigated associations between clinical and dosimetric risk factors and memory outcomes in a cohort of patients treated with proton radiotherapy (PRT). A total of 70 patients (median age at PRT, 12.1 years [range, 5.0-22.5 years]) who were treated with PRT were identified with baseline and follow-up evaluations of visual and verbal memory (Children's Memory Scale and the third edition of the Wechsler Memory Scale). Whole-brain as well as bilateral hippocampal and temporal lobe contours were delineated for the calculation of dosimetric indices. Multivariate analyses were performed to assess associations of score changes over time with clinical factors and dosimetric indices. The median neurocognitive follow-up was 3.0 years (range, 1.1-11.4 years). For the entire cohort, delayed and immediate verbal memory scaled scores demonstrated small declines. The mean decline for delayed verbal memory scores was 0.6 (P = .01), and that for immediate verbal memory scores was 0.5 (P = .06). Immediate and delayed visual memory scores were not found to change significantly (+0.1 and -0.3, respectively; P>.30). A higher left hippocampal V20GyE (percentage of the volume of a particular anatomical region receiving at least a 20 gray equivalent) was correlated with a score decline in all 4 measures. Female sex was found to be predictive of lower delayed verbal memory follow-up scores (P = .035). Only delayed verbal memory scores were found to have declined statistically significantly at follow-up after PRT, reflecting some weakness in verbal memory retrieval. Given a correlation of left hippocampal dosimetry and memory outcomes after PRT, left hippocampal-sparing PRT plans may assist patients with pediatric brain tumors in preserving memory-retrieval abilities. Cancer 2018;124:2238-45. © 2018 American Cancer Society.

A Monte-Carlo study to assess the effect of 1.5 T magnetic fields on the overall robustness of pencil-beam scanning proton radiotherapy plans for prostate cancer

Combining magnetic-resonance imaging (MRI) and proton therapy (PT) using pencil-beam scanning (PBS) may improve image-guided radiotherapy. We aimed at assessing the impact of a magnetic field on PBS-PT plan quality and robustness. Specifically, the robustness against anatomical changes and positioning errors in an MRI-guided scenario with a 30 cm radius 1.5 T magnetic field was studied for prostate PT.Five prostate cancer patients with three consecutive CT images (CT1-3) were considered. Single-field uniform dose PBS-PT plans were generated on the segmented CT1 with Monte-Carlo-based treatment planning software for inverse optimization. Plans were optimized at 90° gantry angle without B-field (no B), with ±1.5 T B-field (B and minus B), as well as at 81° gantry angle and +1.5 T (B G81). Plans were re-calculated on aligned CT2 and CT3 to study the impact of anatomical changes. Dose distributions were compared in terms of changes in DVH parameters, proton range and gamma-index pass-rates. To assess the impact of positioning errors, DVH parameters were compared for ±5 mm CT1 patient shifts in anterior–posterior (AP) and left–right (LR) direction.Proton beam deflection considerably reduced robustness against inter-fractional changes for the B scenario. Range agreement, gamma-index pass-rates and PTV V95% were significantly lower compared to no B. Improved robustness was obtained for minus B and B G81, the latter showing only minor differences to no B. The magnetic field introduced slight dosimetric changes under LR shifts. The impact of AP shifts was considerably larger, and equivalent for scenarios with and without B-field.Results suggest that robustness equivalent to PT without magnetic field can be achieved by adaptation of the treatment parameters, such as B-field orientation (minus B) with respect to the patient and/or gantry angle (B G81). MRI-guided PT for prostate cancer might thus be implemented without compromising robustness compared to state-of-the-art CT-guided PT.

Monte Carlo-driven predictions of neurocognitive and hearing impairments following proton and photon radiotherapy for pediatric brain-tumor patients.

As proton radiotherapy (RT) remains a limited resource, predictive estimates of the potential reduction in adverse treatment-related outcomes compared to photon RT could potentially help improve treatment selection. The aim of this study was to predict the magnitude of the neurocognitive and hearing deficits associated with proton and photon RT for children with brain tumors. The existing RT plans for 50 children treated with photon intensity modulated RT were compared with generated intensity modulated proton RT plans. The proton and photon RT dose distribution was used to estimate the Full Scale Intelligence Quotient (IQ) via a Monte Carlo model and the probability of hearing loss per ear, based on previously published dose-risk relationships. Compared to photon plans, the mean brain dose was found to be reduced in all proton plans, translating into a gain of [Formula: see text] IQ points for the whole cohort at 5years post-RT for dose regimens of 54Gy, or [Formula: see text] IQ points for dose regimens of 59.4Gy, where the errors shown represent statistical and systematic uncertainties. The probability of hearing loss ≥20dB per ear was less for proton versus photon RT: overall (9 ± 4) versus (17 ± 6)%, respectively, based on dose regimens of 54Gy, and (13 ± 5) versus (23 ± 9)% for dose regimens of 59.4Gy. Proton RT is thus expected to reduce the detrimental effect of RT upon IQ and hearing as compared to photon RT for pediatric brain tumors.

Fast imaging employing steady-state acquisition (FIESTA) MRI to investigate cerebrospinal fluid (CSF) within dural reflections of posterior fossa cranial nerves.

There is no consensus approach to covering skull base meningeal reflections-and cerebrospinal fluid (CSF) therein-of the posterior fossa cranial nerves (CNs VII-XII) when planning radiotherapy (RT) for medulloblastoma and ependymoma. We sought to determine whether MRI and specifically fast imaging employing steady-state acquisition (FIESTA) sequences can answer this anatomical question and guide RT planning. 96 posterior fossa FIESTA sequences were reviewed. Following exclusions, measurements were made on the following scans for each foramen respectively (left, right); internal acoustic meatus (IAM) (86, 84), jugular foramen (JF) (83, 85) and hypoglossal canal (HC) (42, 45). A protocol describes measurement procedure. Two observers measured distances for five cases and agreement was assessed. One observer measured all the remaining cases. IAM and JF measurement interobserver variability was compared. Mean measurement difference between observers was -0.275 mm (standard deviation 0.557). IAM and JF measurements were normally distributed. Mean IAM distance was 12.2 mm [95% confidence interval (CI) 8.8-15.6]; JF was 7.3 mm (95% CI 4.0-10.6). The HC was difficult to visualize on many images and data followed a bimodal distribution. Dural reflections of posterior fossa CNs are well demonstrated by FIESTA MRI. Measuring CSF extension into these structures is feasible and robust; mean CSF extension into IAM and JF was measured. We plan further work to assess coverage of these structures with photon and proton RT plans. Advances in knowledge: We have described CSF extension beyond the internal table of the skull into the IAM, JF and HC. Oncologists planning RT for patients with medulloblastoma and ependymoma may use these data to guide contouring.

Implementation of an analytical model for leakage neutron equivalent dose in a proton radiotherapy planning system.

Equivalent dose from neutrons produced during proton radiotherapy increases the predicted risk of radiogenic late effects. However, out-of-field neutron dose is not taken into account by commercial proton radiotherapy treatment planning systems. The purpose of this study was to demonstrate the feasibility of implementing an analytical model to calculate leakage neutron equivalent dose in a treatment planning system. Passive scattering proton treatment plans were created for a water phantom and for a patient. For both the phantom and patient, the neutron equivalent doses were small but non-negligible and extended far beyond the therapeutic field. The time required for neutron equivalent dose calculation was 1.6 times longer than that required for proton dose calculation, with a total calculation time of less than 1 h on one processor for both treatment plans. Our results demonstrate that it is feasible to predict neutron equivalent dose distributions using an analytical dose algorithm for individual patients with irregular surfaces and internal tissue heterogeneities. Eventually, personalized estimates of neutron equivalent dose to organs far from the treatment field may guide clinicians to create treatment plans that reduce the risk of late effects.

Evaluation of normal tissue exposure in patients receiving radiotherapy for pancreatic cancer based on RTOG 0848.

Pancreatic cancer is a highly aggressive malignancy. Chemoradiotherapy (CRT) is utilized in many cases to improve locoregional control; however, toxicities associated with radiation can be significant given the location of the pancreas. RTOG 0848 seeks to evaluate chemoradiation using either intensity-modulated radiation therapy (IMRT) or 3D conformal photon radiotherapy (3DCRT) modalities as an adjuvant treatment. The purpose of this study is to quantify the dosimetric changes seen when using IMRT or 3D CRT photon modalities, as well as proton radiotherapy, in patients receiving CRT for cancer of the pancreas treated per RTOG 0848 guidelines. Ten patients with pancreatic head adenocarcinoma treated between 2010 and 2013 were evaluated in this study. All patients were simulated with contrast-enhanced CT imaging. Separate treatment plans using IMRT and 3DCRT as well as proton radiotherapy were created for each patient. All planning volumes were created per RTOG 0848 protocol. Dose-volume histograms (DVH) were calculated and analyzed in order to compare plans between the three modalities. The organs at risk (OAR) evaluated in this study are the kidneys, liver, small bowel, and spinal cord. There was no difference between the IMRT and 3DCRT plans in dose delivered to the kidneys, liver, or bowel. The proton radiotherapy plans were found to deliver lower mean total kidney doses, mean liver doses, and liver D1/3 compared to the IMRT plans. The proton plans also gave less mean liver dose, liver D1/3, bowel V15, and bowel V50 in comparison to the 3DCRT. For patients receiving radiotherapy per ongoing RTOG 0848 for pancreatic cancer, there was no significant difference in normal tissue sparing between IMRT and 3DCRT treatment planning. Therefore, the choice between the two modalities should not be a confounding factor in this study. The proton plans also demonstrated improved OAR sparing compared to both IMRT and 3DCRT treatment plans.

FoCa: a modular treatment planning system for proton radiotherapy with research and educational purposes

FoCa is an in-house modular treatment planning system, developed entirely in MATLAB, which includes forward dose calculation of proton radiotherapy plans in both active and passive modalities as well as a generic optimization suite for inverse treatment planning.The software has a dual education and research purpose. From the educational point of view, it can be an invaluable teaching tool for educating medical physicists, showing the insights of a treatment planning system from a well-known and widely accessible software platform. From the research point of view, its current and potential uses range from the fast calculation of any physical, radiobiological or clinical quantity in a patient CT geometry, to the development of new treatment modalities not yet available in commercial treatment planning systems.The physical models in FoCa were compared with the commissioning data from our institution and show an excellent agreement in depth dose distributions and longitudinal and transversal fluence profiles for both passive scattering and active scanning modalities. 3D dose distributions in phantom and patient geometries were compared with a commercial treatment planning system, yielding a gamma-index pass rate of above 94% (using FoCa’s most accurate algorithm) for all cases considered.Finally, the inverse treatment planning suite was used to produce the first prototype of intensity-modulated, passive-scattered proton therapy, using 13 passive scattering proton fields and multi-leaf modulation to produce a concave dose distribution on a cylindrical solid water phantom without any field-specific compensator.

SU-E-T-555: A Protontherapy Inverse Treatment Planning System Prototype with Linear Energy Transfer (LET) Optimization

Purpose: Develop and benchmark an inverse treatment planning system (TPS) for proton radiotherapy integrating fast analytical dose and LET calculations in patient geometries and a dual objective function with both dose and LET components, enabling us to apply optimization techniques to improve the predicted outcome of treatments based on radiobiological models. Methods: The software package was developed in MATLAB and implements a fluence-dose calculation technique based on a pencil beam model for dose calculations and a 3D LET model based on the extension of the LET in the radial direction as a function of the predicted radiological pathway. Both models were benchmarked against commissioning data from our institution, dose calculations performed with a commercial treatment planning system and Monte Carlo simulations. The optimization is based on the adaptive simulated annealing approach . Results: The dose and LET calculations were tested in a water phantom and several real patient treatments. The pass rate for the gamma index analysis (3%/3mm) test was above 90% for all test cases analyzed, and the calculation time was of the order of seconds. The inverse planning module produced plans with a significantly higher mean LET in the target compared to traditional plans, without any loss of target coverage. The clinical relevance of this improvement is under consideration . Conclusion: The developed treatment planning system is a valuable clinical and research tool that enables us to incorporate LET effects into proton radiotherapy planning in a streamlined fashion.