Anterior Oblique Beams Research Articles

The Role of Proton Therapy for Prostate Cancer in the Setting of Hip Prosthesis.

Given that the current standard of proton therapy (PT) for prostate cancer is through bilateral beams, this modality is typically avoided when it comes to treatment of patients with hip prosthesis. The purpose of this study was to evaluate whether novel PT methods, i.e., anterior proton beams and proton arc therapy (PArc), could be feasible options to treat this patient subpopulation. We evaluate PT methods in the context of dosimetry and robustness and compare with standard of practice volumetric modulated arc therapy (VMAT) to explore any potential benefits. Two PT and one VMAT treatment plans were retrospectively created for 10 patients who participated in a clinical trial with a weekly repeat CT (rCT) imaging component. All plans were robustly optimized and featured: (1) combination anterior oblique and lateral proton beams (AoL), (2) PArc, and (3) VMAT. All patients had hydrogel spacers in place, which enabled safe application of anterior proton beams. The planned dose was 70 Gy (RBE) to the entire prostate gland and 50 Gy (RBE) to the proximal seminal vesicles in 28 fractions. Along with plan dose-volume metrics, robustness to setup and interfractional variations were evaluated using the weekly rCT images. The linear energy transfer (LET)-weighted dose was evaluated for PArc plans to ensure urethra sparing given the typical high-LET region at the end of range. Both PT methods were dosimetrically feasible and provided reduction of some key OAR metrics compared to VMAT except for penile bulb, while providing equally good target coverage. Significant differences in median rectum V35 (22-25%), penile bulb Dmean (5 Gy), rectum V61 (2%), right femoral head Dmean (5 Gy), and bladder V39 (4%) were found between PT and VMAT. All plans were equally robust to variations. LET-weighted dose in urethra was equivalent to the physical dose for PArc plans and hence no added urethral toxicity was expected. PT for treatment of prostate cancer patients with hip prosthesis is feasible and equivalent or potentially superior to VMAT in quality in some cases. The choice of radiotherapy regimen can be personalized based on patient characteristics to achieve the best treatment outcome.

The effect of common dental fixtures on treatment planning and delivery for head and neck intensity modulated proton therapy.

Proton treatment plan perturbation by common dental fixtures such as amalgams (Am) and porcelain-fused-to-metal (PFM) crowns has, to date, been uncharacterized. Previous studies have been conducted to determine the physical effect of these materials within the beam path for single spots, but their effects on complex treatment plans and clinical anatomy have not yet been quantified. The present manuscript aims to study the effect of Am and PFM fixtures on proton treatment planning in a clinical setting. An anthropomorphic phantom with removable tongue, maxilla, and mandible modules was simulated on a clinical computed tomography (CT) scanner. Spare maxilla modules were modified to include either a 1.5mm depth central groove occlusal amalgam (Am) or a porcelain-fused-to-metal (PFM) crown, implanted on the first right molar. Modified tongue modules were 3D printed to accommodate several axial or sagittal oriented pieces of EBT-3 film. Clinically representative spot-scanning proton plans were generated in Eclipse v.15.6 using the proton convolution superposition (PCS) algorithm v.15.6.06 using a multi-field optimization (MFO) technique with the goal of delivering a uniform 54Gy dose to a clinical target volume (CTV) typical of a base-of-tongue (BoT) treatment. A typical geometric beam arrangement of two anterior oblique (AO) beams and a posterior beam was employed. Plans optimized without any material overrides were delivered to the phantom A) without implants; B) with Am fixture; or C) with PFM crown. Plans were also reoptimized and delivered with inclusion of material overrides to equate relative stopping power of the fixture with that of a previously measured result. Plans exhibit slightly greater dose weight towards AO beams. The optimizer accounted for inclusion of fixture overrides by increasing beam weights to the beam closest to the implant. Film measurements exhibited cold spots directly within the beam path through the fixture in plans with and without overridden materials. Cold spots were somewhat mitigated in plans including overridden materials in the structure set but were not entirely eliminated. Cold spots associated with Am and PFM fixtures were quantified at 17% and 14% for plans without overrides, respectively, and 11% and 9% with using Monte Carlo simulation. Compared with film measurements and Monte Carlo simulation, the treatment planning system underestimates the dose shadowing effect in plans including material overrides. Dental fixtures create a dose shadowing effect directly in line with the beam path through the material. This cold spot is partially mitigated by overriding the material to measured relative stopping powers. Due to uncertainties in modeling perturbation through the fixture, the magnitude of the cold spot is underestimated using the institutional TPS when compared to measurement and MC simulation.

Dosimetric and Clinical Features Associated with Replan in Proton Head and Neck Therapy

Intensity modulated proton therapy has become increasingly popular in the treatment of head and neck (HN) cancer because of its high normal tissue sparing compared to photon therapy. However, proton plans are very sensitive to anatomy changes such as weight loss or tumor shrinkage that leads to a 25% replan rate at our center. This analysis aims to predict whether a HN patient will need a replan using various dosimetric and clinical features at the onset of treatment.Data were gathered from 176 HN patients treated at our institution. The most common sites were the oropharynx (40 cases), lip/oral cavity (20 cases), and nasal cavity/sinuses (14 cases). Beam dose heterogeneity index (BHI) was defined as the ratio of the D0.1cc of beam dose to half of the prescription dose. BHI was calculated for every beam and the average BHI for each plan was calculated. Robustness scenarios included a combination of ± 3 mm setup shifts on 3 coordinate directions and ± 3.5% range uncertainty. Plan robustness was evaluated with several features gathered from the highest dose level CTV. These include the fraction of all scenarios where V100 > 95% (passing rate), mean V100, mean V100 deviation from the nominal plan, and mean max dose change from the nominal. 61% of patients were treated to bilateral neck with multi-dose level simultaneous integrated boost plans. A five-beam arrangement (two posterior, two anterior oblique beams, and an AP beam) were used to treat most bilateral HN patients and a 3-beam arrangement was used to treat most unilateral HN patients. Any portion of the target is typically covered by at least two beams.Sixty-three patients were replanned at least once in this subpopulation. Plans were normalized at V100 = 98% when possible for the highest dose level. The BHIs from each planner were significantly different from each other, ranging from 1.01 to 1.27 (P = 0.003). Planner re-plan rates (ranging from 11%-42%) significantly correlate with their BHIs, r = 0.747 (P = 0.03). BHI for re-planned patients was higher than non-replan patients:1.11 ± 0.09 vs. 1.06 ± 0.16 (P = 0.017). The only significant robustness feature was the mean max dose change:3.1 ± 1.3% vs. 2.5 ± 1.4% (P = 0.038).We have identified several features that correlate strongly with HN replans. A fine-tuned planning protocol is being developed to reduce the BHI for all HN plans. Our future work is to build a deep-learning model based on our current features and others such as patients' clinical tumor information, planning image, plan conformity, etc., to predict the probability of a replan before treatment.

Early-Stage Glottic Squamous Cell Carcinoma in the Era of Image-Guided Radiotherapy.

Early-stage squamous cell cancer (SCC) of the glottis has a good prognosis. Therefore, patients have long survival outcomes and may potentially suffer from late toxicities of radiotherapy. Radiotherapy with a conventional parallel-opposed-pair or anterior-oblique beam arrangements for stage 1 and 2 glottic SCC have field borders that traditionally cover the entire larynx, exposing organs-at-risk (e.g. carotid arteries, contralateral vocal cord, contralateral arytenoid and inferior pharyngeal constrictor muscles) to high radiation doses. The potential long-term risk of cerebrovascular events has attracted much attention to the dose that carotid arteries receive. Swallow and respiratory motion of laryngeal structures has been an important factor that previously limited reduction of the radiation treatment volume. Motion has been evaluated using multiple imaging modalities and this information has been used to calculate PTV margins for generation of more limited target volumes. This review discusses the current literature surrounding dose-effect relationships for various organs-at-risk and the late toxicities that are associated with them. This article also reviews the currently available data and effects of laryngeal motions on dosimetry to the primary target. We also review the current limitations and benefits of a more targeted approach of radiotherapy for early-stage glottic SCCs and the evolution of CT-based IGRT and MR-guided radiotherapy techniques that may facilitate a shift away from a conventional 3D-conformal radiotherapy approach.

Fabrication and development of a thorax phantom to evaluate 3D CRT treatment planning techniques for post-mastectomy chest wall radiotherapy.

The aim of this study was to design and fabricate a thorax phantom to quantify the radiation doses to the region of the chest wall (with 3 ionization chambers), the organ at risk (OAR) (lung), and the surface using radiochromic films (EBT3) for three different 3D CRT treatment planning techniques. Anthropomorphic phantoms are one of the best tools for verifying the quality of the radiotherapy treatment plans generated by treatment planning systems since they can provide equivalent human tissue densities. Thirty acrylic plates were cut into ellipses 21cm in height and 31cm in width, and slots were created to insert lung equivalent cork material and bone equivalent Teflon material. Three treatment planning techniques were designed: (A) tangential pair beams, (B) tangential pair beams with wedges and (C) tangential beams followed by an anterior oblique beam. The percentage difference between the measured point doses and the calculated doses (measured with three CC13 ionization chambers) ranged from - 3.2 to 1.6%, with a mean deviation of - 1.04 ± 1.3%. The measured mean percentage doses on the target surface with EBT3 film were 90.3% and 95.1% of the prescribed dose with 5-mm and 10-mm boluses, respectively. Finally, the average absolute dose difference between the measured and calculated surface doses was within 10cGy in all three planning techniques. The developed thorax phantom is suitable for point dose measurements using ionization chambers and for surface dose measurements using EBT3 Gafchromic films in post-mastectomy chest wall radiotherapy.

Outcomes of and Treatment Planning Considerations for A Novel Technique Delivering Proton Pencil-Beam Scanning Radiation to Women With Metal-Containing Tissue Expanders Undergoing Post-Mastectomy Radiation

Breast reconstructive tissue expanders (TEs) contain metallic ports (MCPs) comprised of high “Z” materials. This presents a challenge for proton pencil-beam scanning (PBS) planning given potential dose attenuation and concern for port movement. We hypothesize that a novel technique utilizing hybrid single- and multi-field optimizations (SFO, MFO) for delivering post-mastectomy radiation (PMRT) using proton PBS for patients with TEs and MCPs will be robust and uphold the dosimetric benefits of proton therapy. A protocol utilizing a hybrid SFO/MFO technique was prospectively developed. Plans were robustly optimized using a Monte Carlo algorithm. A CTV_eval structure including chest wall (CW) and regional nodal (RNI) targets and excluding boost plans and the TE metallic components plus a 1 cm margin was evaluated for target coverage, robustness, and dose homogeneity. Thirteen women with TEs completed PMRT between 2/12/19 and 1/2/20. Median age was 46 years (range, 37-60), 67% were white. Median body-mass index (BMI) was 24 (range, 19-36). 75% of patients had left-sided disease. A 2 or 3-field SFO technique was used superior and inferior to the MCP, while a 3 or 4-field MFO technique was used at the level of the MCP. At the level of the MCP, beams were blocked to deliver dose anterior/posterior and lateral to the port without going through it. A port-to-CW distance of 1cm was required to deliver dose posteriorly. Anterior, anterior oblique, and lateral beam angles were utilized. Anterior beams were given with a couch kick to enter under the breast and deliver dose behind the expander. Patients underwent daily image-guidance to ensure the port remained within a 5mm planning volume (PRV). The median total RT dose to CTV_eval was 50.4Gy (45.0-50.4) delivered in 1.8Gy/fraction; 5 (38%) of plans utilized a boost. Median ipsilateral lung V20 was 20% (2.0-29); median average heart dose was 1.7Gy (0.5-3.5). Median 100% CTV_eval coverage was 95% (90-95) with a median homogeneity index of 4.2(1.9-18). OSLD readings anterior to the port were performed on 5 patients and correlated to the dose measurements in the TPS. When evaluating plan robustness, median worst-case 95% CTV_eval coverage was 95% (90-97%). There was one ≥ G2 acute toxicity of G4 skin necrosis in a patient with very thin tissue flaps which did not occur immediately anterior to the port but required expander removal. At a median follow up of 3.0 months, 2 patients had successful permanent reconstructions after RT completion. Delivering PMRT with PBS for women with metal-containing TEs using a novel hybrid SFO/MFO technique is feasible, robust, achieves excellent dose distributions to targets and OARs, and did not lead to unexpected toxicities. Additional dosimetric, physics and set up techniques are required to safely deploy this treatment in the clinic. This is the largest series to date describing the delivery of PMRT to women with MCPs, and suggests that MCPs may not preclude treatment with PBS.

Dosimetric Analysis of a Longitudinal Clinical Experience Using Robotic Radiosurgery and LINAC-based SBRT with VMAT for Early-Stage Non-Small Cell Lung Cancer (ES-NSCLC)

SBRT is standard of care for medically inoperable patients with ES-NSCLC and can be delivered using robotic radiosurgery or standard linear accelerator (LINAC) platforms. CK uses hundreds of anterior oblique non-coplanar beams while LINAC SBRT commonly uses volumetric modulated arc therapy (VMAT) with multiple coplanar full or partial arc fields. SBRT plans are designed to cover the PTV in prescription dose while achieving steep dose fall-off in adjacent tissue which causes increased dose heterogeneity “i.e., hotspots” in the target volume. We aimed to compare the dosimetric characteristics of lung SBRT plans delivered at one institution based on CK vs LINAC VMAT technique. Patients were included who received CK-based (2012-16) or LINAC-based SBRT from (2016-17) for T1-2N0M0 NSCLC. SBRT plans of 198 patients who met inclusion criteria were analyzed (CK, n=149 and LINAC, n=59). CK plans were computed using Monte Carlo algorithm, while the LINAC-based VMAT plans were computed in collapsed cone convolution-superposition algorithm. All clinically delivered plans were reviewed to extract dosimetric parameters including target volume coverage and OARs dose distribution. Differences in mean dosimetric values by technique were estimated via Wilcoxon Rank-Sum Test. Multivariate analyses were run using logistical regression to test for confounding variables. LINAC SBRT was prescribed to a higher mean isodose line (IDL) (89% vs 80%, p<.001) yet had increased mean ratios of GTVmax (131% vs 125%, p<.001), GTVmean (120% vs 116%, p<.001), PTVmax (132% vs 126%, p<.001), and D90GTV (114% vs 111%, p<.001) doses to prescription dose compared to CK. LINAC-based SBRT had lower mean conformality index (1.10 vs. 1.21, p <.001) than CK, but there was no difference in mean R50 values (5.06 vs. 4.88, p=.67). Mean ratio of PTV to total lung volume did not differ significantly for LINAC SBRT vs. CK (1.17% vs. 1.54%, p=.08), but LINAC SBRT was associated with lower average lung V5 (18% vs. 25%, p<.001), V10 (11% vs. 14%, p=.02), mean lung dose (3.7 Gy vs. 5.1 Gy, p<.001) and lung volume (cc) receiving <12.5 Gy (3980 cc vs. 3300 cc, p=.002) than CK. LINAC SBRT was also associated with lower heart mean doses compared to CK (1.8 Gy vs. 2.5 Gy, p=.004) and heart V5 (12.7% vs. 19.5%, p=.009). There was no difference in max dose to the proximal bronchial tree. On multivariate analysis controlling for total dose, lung volume, PTV size, and target lobe the differences in lung V5 (p <.001) and mean lung dose (p <.001) by technique persisted but differences in lung cc receiving <12.5 Gy, lung V10, heart V5 and heart mean dose were no longer statistically significant. Despite being prescribed to higher mean IDLs, LINAC SBRT with VMAT technique delivered higher doses to the GTV and PTV as compared to CK and was associated with lower lung V5 and mean lung dose but not lower lung V10 or V20.

Comparison of radiotherapy techniques to reduce hematologic toxicity in whole pelvic radiation therapy

Introduction: Concurrent chemoradiotherapy (CRT) is a standard treatment method for patients with carcinoma of cervix. Despite admirable therapeutic results, acute hematologic toxicity (HT) is common with this regimen. Many studies evaluate the relationship between the bone marrow dosimetric parameters and the severity of HT and result shown that the low dose of bone marrow would decrease the incidence of HT in patient undergoing concomitant CRT. In this study the dosimetric parameters of two radiotherapy plans in managing of cervix cancer has been evaluated to investigate the best plan on the way of reducing bone marrow dose. Materials and Methods: Computed tomography scans of 18 patients with carcinoma of cervix were acquired and transferred to the 3D treatment planning system. The corePlan3D treatment planning system was used to contour all of the structures and to compute the dose distribution for plans based on collapsed cone convolution (CCC). For each patient, two different treatment plan were prepared using 15 MV photon energies. The minimum dose (Dmin), maximum dose (Dmax) and mean dose (Dmean) to target (PTV) and femoral head were compared for each plan. Results: Result shown that our manipulated four-field plan which use anterior oblique beams seemed to deliver a lower mean dose to femoral head against conventional box fields (Dmean=66.7±3.1 cGy, 98.8±7.3 cGy, Dmax=117.5±3.0 cGy, 126.9±4.3 cGy, respectively) and deliver sufficient dose to PTV (Dmax=213.5±4.2 cGy, 194.6±2.0 cGy, respectively). Conclusion: With suspicious planning in respect to choice of beam angles, beam weighting, and appreciation of potential exposure of normal tissues to exit dose, this study revealed that compared with conventional box fields, anterior oblique beams can achieve significant reductions in the dose to BM with adequate dose coverage to the PTV with an accurate beam arrangement

Impact of interfractional motion on hypofractionated pencil beam scanning proton therapy and VMAT delivery for prostate cancer.

Hypofractionated radiotherapy of prostate cancer is gaining clinical acceptance given its potential increase in therapeutic ratio and evidence for noninferiority and lack of added late toxicities compared to conventional fractionation. However, concerns have been raised that smaller number of fractions might lead to larger dosimetric influence by interfractional motion. We aim to compare the effect of these variations on hypofractionated pencil beam scanning (PBS) proton therapy and volumetric modulated arc therapy (VMAT) for localized prostate cancer. Weekly CT images were acquired for 6 patients participating in a randomized clinical trial. PBS plans featuring bilateral (BL) and a combination of lateral and anterior-oblique beams (AOL), and VMAT plans were created. All patients were treated to a conventional 79.2Gy total dose in 44 fractions. For this study, hypofractionated dose to the prostate gland was 51.6Gy in 12 fractions or 36.25Gy in 5 fractions, and 32.8, and 23.1Gy to proximal seminal vesicles, respectively. Patients were simulated with endorectal balloons to aid gland immobilization. Three fiducial markers were implanted for setup guidance. All plans were recomputed on the weekly CT images after aligning with the simulation CT. The entire set of 9 CT images was used for dose recalculation for 12-fraction and only 5 used for the 5-fraction case. Adaptive range adjustments were applied to anterior-oblique beams assuming clinical availability of invivo range verification. Fractional doses were summed using deformable dose accumulation to approximate the delivered dose. Biologically equivalent dose to 2Gy(EQD2) was calculated assuming α/β of 1.5Gy for prostate and 3Gy for bladder and rectum. The median delivered prostate D98 was 0.13/0.14/0.13Gy(EQD2) smaller than planned for PBS-BL, 0.13/0.27/0.17Gy(EQD2) for PBS-AOL and 0.59/0.66/0.59Gy(EQD2) for VMAT, for 44/12/5 fractions, respectively. The largest D98 reduction was 1.5 and 3.5Gy(EQD2) for CTV1 and CTV2, respectively. Target dose degradation was comparable for all fractionation schemes within each modality. The maximum increase in rectum D2 was 0.98Gy(EQD2) for a 5-fraction PBS case. The robustness of PBS and VMAT were comparable for all patients for the studied fractionations. The delivered target dose generally remained within clinical tolerance and the deviations were relatively minor for both fractionation schemes. The delivered OAR dose stayed in compliance with the RTOG hypofractionation constraints for all cases.

Radiation Therapy Field Design and Lymphedema Risk After Regional Nodal Irradiation for Breast Cancer

The occurrence of upper extremity lymphedema after regional nodal irradiation (RNI) for breast cancer treatment varies significantly based on patient and treatment factors. The relationship between the radiation therapy (RT) field design and lymphedema risk is not well-characterized. The present study sought to correlate the variations in RT field design with lymphedema outcomes. Women with stage II-IV breast cancer receiving RNI after breast surgery that included sentinel lymph node biopsy or axillary dissection were identified. Their arm circumference was measured before RT and at each follow-up visit to assess for lymphedema. Nodal RT fields were defined using a trifurcated system. Group 1 excluded the upper level I and II axilla, defined by the lateral border of the nodal field encompassing less than one-third of the humeral head. Group 2 included the upper level I and II axilla, defined by the lateral border of the nodal field encompassing more than one-third of the humoral head treated with an anterior oblique beam. Group 3 included the upper level I and II axilla the same as for group 2 but with parallel-opposed beams delivering a significant dose to the musculature posterior to the axilla. From 1999 to 2013, 526 women received RNI. The median post-RT follow-up was 5.5years. For the 492 women meeting the inclusion criteria, the cumulative incidence of lymphedema was 23.5% at 2years and 31.8% at 5years. On univariate analysis, the patients in group 1 had a lower 5-year lymphedema rate (7.7%) than those in group 2 (37.1%) and group 3 (36.7%; P<.0001). On multivariate analysis, inclusion of the upper level I and II axilla (groups 2 and 3) remained significantly associated with increased lymphedema risk. Variations in the RT field design significantly affect the development of lymphedema after RNI. In particular, the upper level I and II axilla appear to be important regions for lymphedema risk after axillary dissection.

Proton therapy of prostate cancer by anterior-oblique beams: implications of setup and anatomy variations

Proton therapy of prostate by anterior beams could offer an attractive option for treating patients with hip prosthesis and limiting the high-dose exposure to the rectum. We investigated the impact of setup and anatomy variations on the anterior-oblique (AO) proton plan dose, and strategies to manage these effects via range verification and adaptive delivery. Ten patients treated by bilateral (BL) passive-scattering proton therapy (79.2 Gy in 44 fractions) who underwent weekly verification CT scans were selected. Plans with AO beams were additionally created. To isolate the effect of daily variations, initial AO plans did not include range uncertainty margins. The use of fixed planning margins and adaptive range adjustments to manage these effects was investigated. For each case, the planned dose was recalculated on weekly CTs, and accumulated on the simulation CT using deformable registration to approximate the delivered dose. Planned and accumulated doses were compared for each scenario to quantify dose deviations induced by variations. The possibility of estimating the necessary range adjustments before each treatment was explored by simulating the procedure of a diode-based in vivo range verification technique, which would potentially be used clinically. The average planned rectum, penile bulb and femoral heads mean doses were smaller for initial AO compared to BL plans (by 8.3, 16.1 and 25.9 Gy, respectively). After considering interfractional variations in AO plans, the target coverage was substantially reduced. The maximum reduction of V79.2/D95/Dmean/EUD for AO (without distal margins) (25.3%/10.7/1.6/4.9 Gy, respectively) was considerably larger than BL plans. The loss of coverage was mainly related to changes in water equivalent path length of the prostate after fiducial-based setup, caused by discrepancies in patient anterior surface and bony-anatomy alignment. Target coverage was recovered partially when using fixed planning margins, and fully when applying adaptive range adjustments. The accumulated organs-at-risk dose for AO beams after range adjustment demonstrated full sparing of femoral heads and superior sparing of penile bulb and rectum compared to the conventional BL cases. Our study indicates that using AO beams makes prostate treatment more susceptible to target underdose induced by interfractional variations. Adaptive range verification/adjustment may facilitate the use of anterior beam approaches, and ensure adequate target coverage in every fraction of the treatment.

Quantifying radiation dose delivered to individual shoulder muscles during breast radiotherapy

Background and purposeRadiotherapy is an effective treatment for managing breast cancer, but patients may experience shoulder morbidity after completing radiotherapy. There is a knowledge gap regarding how the inclusion of the regional lymphatics in radiation treatment regimens influence the radiation dose delivered to the underlying shoulder musculature. Material and methodsFive standardized radiation treatment regimens were developed from the computed tomography (CT) scans of 11 patients: tangent fields only (T), high tangent fields (HT), T+supraclavicular fossa and axillary apex with an anterior oblique beam (SCV), T+SCV+axillary nodes with an anterior oblique beam (SCV+AX), and T+SCV+AX with the nodal regions treated with a directly opposed beam configuration (DO). The muscle volumes for nine shoulder muscles anatomically located with the treatment regimens were segmented from the same CT scans. The effect of the nine muscles and five treatment regimens on the percentage of each muscle receiving at least 48Gy (V48Gy) was analyzed with two-way and one-way repeated measures ANOVAs. ResultsA statistically significant interaction existed between the nine shoulder muscles and five treatment regimens (p<0.001) on the V48Gy dose. Subsequent one-way analyses found statistically significant main effects of treatment plan on the V48Gy dose for each muscle (p<0.001). The pectoralis major and minor had the greatest V48 doses across the five treatments regimens. The HT, SCV+AX and DO treatment regimens produced statistically significant increases in the V48 dose of the latissimus dorsi and teres major. The infraspinatus, subscapularis, supraspinatus, teres minor, and trapezius only observed statistically significant V48 doses when treated with a DO plan. ConclusionsThese findings highlight the muscles (pectoralis major, pectoralis minor, latissimus dorsi, and teres major) that may exhibit future morbidity after radiation, and indicate that nodal RT delivered with a DO beam arrangement delivers the highest muscle dose.

Hydrogel rectum-prostate spacers mitigate the uncertainties in proton relative biological effectiveness associated with anterior-oblique beams

Aim: Anterior-oblique (AO) proton beams can form an attractive option for prostate patients receiving external beam radiotherapy (EBRT) as they avoid the femoral heads. For a cohort with hydrogel prostate-rectum spacers, we asked whether it was possible to generate AO proton plans robust to end-of-range elevations in linear energy transfer (LET) and modeled relative biological effectiveness (RBE). Additionally we considered how rectal spacers influenced planned dose distributions for AO and standard bilateral (SB) proton beams versus intensity-modulated radiotherapy (IMRT).Material and methods: We studied three treatment strategies for 10 patients with rectal spacers: (A) AO proton beams, (B) SB proton beams and (C) IMRT. For strategy (A) dose and LET distributions were simulated (using the TOPAS Monte Carlo platform) and the McNamara model was used to calculate proton RBE as a function of LET, dose per fraction, and photon α/β. All calculations were performed on pretreatment scans: inter- and intra-fractional changes in anatomy/set-up were not considered.Results: For 9/10 patients, rectal spacers enabled generation of AO proton plans robust to modeled RBE elevations: rectal dose constraints were fulfilled even when the variable RBE model was applied with a conservative α/β = 2 Gy. Amongst a subset of patients the proton rectal doses for the planning target volume plans were remarkably low: for 2/10 SB plans and 4/10 AO plans, ≤10% of the rectum received ≥20 Gy. AO proton plans delivered integral doses a factor of approximately three lower than IMRT and spared the femoral heads almost entirely.Conclusion: Typically, rectal spacers enabled the generation of anterior beam proton plans that appeared robust to modeled variation in RBE. However, further analysis of day-to-day robustness would be required prior to a clinical implementation of AO proton beams. Such beams offer almost complete femoral head sparing, but their broader value relative to IMRT and SB protons remains unclear.

SU‐F‐T‐214: Re‐Thinking the Useful Clinical Beam Energy in Proton Therapy: An Opportunity for Cost Reduction

Purpose:We conducted a retrospective study of the useful clinical proton beam energy based on the beam range data of patients treated over the last 10 years at Massachusetts General Hospital Proton Therapy Center.Methods:Treatment field information were collected for all patients treated over the last 10 years (2005–2015) in the two gantry treatment rooms at MGH. The beam ranges for these fields were retrieved and categorized per treatment site. The 10 prostate patients that required the highest beam range (lateral fields) were selected. For these patients, anterior oblique beams (30–40 degrees) were simulated in a planning system to obtain the required beam ranges including the margins for potential range uncertainties.Results:There were a total of 4033 patients, treated with combined total of 23603 fields. All treatment indications were considered with the exception of ocular tumors generally treated in a fixed beam room. For all non‐prostate treatments (21811 fields), only 5 fields for 4 patients (1‐pancreas, 1‐lumbar chordoma, 2‐spine mets) required beam range greater than 25 cm. There were 446 prostate patients (1792 fields), with the required beam range from 22.3 to 29.0 cm; 386 of them had at least one of their lateral beam range greater than 25 cm. For the 10 prostate patients with highest lateral beam ranges (26 to 29 cm), their treatment with anterior oblique beams would drop the beam ranges below 25 cm (17.3 to 18.5 cm).Conclusion:if prostate patients are treated with anterior fields only, the useful maximum beam range is reduced to 25 cm. Thus a proton therapy system with maximum beam energy of 196 MeV is sufficient to treat all tumors sites with very rare exceptions (&lt;0.1%). Designing such PT system would reduce the cost of proton therapy for hospitals and patients and increase the accessibility to the treatment.

SU‐G‐JeP4‐09: Impact of Interfractional Motion On Hypofractionated Pencil Beam Scanning Proton Therapy for Prostate Cancer

Purpose:To investigate the impact of anatomy/setup variations on standard vs. hypofractionated anterolateral pencil beam scanning (PBS) proton therapy for prostate cancer.Methods:Six prostate cancer patients treated with double‐scattering proton therapy, who underwent weekly verification CT scans were selected. Implanted fiducials were used for localization, and endorectal balloons for immobilization. New PBS plans using combination of lateral and anterior‐oblique (AO) (±35 deg) beams were created. AO beams were added to spare the femoral heads during hypofractionation. Lateral beams delivered 50.4 Gy(RBE) to prostate plus 5‐15mm of seminal vesicles and AO beams 28.8 Gy(RBE) to prostate, in 44 fractions. PTV was laterally expanded by 2.5% to account for range uncertainty. No range margins were applied for AO beams, assuming delivery with in‐vivo range verification. Field‐specific apertures with 1.2cm margin were used. Spot size was ∼9.5mm sigma for 172MeV @isocenter in air. Plans were optimized as single‐field‐uniform‐dose with ∼5% maximum non‐uniformity. The planned dose was recomputed on each weekly CT after aligning the fiducials with the simulation CT, scaled and accumulated via deformable image registration. Hypofractionated treatments with 12 and 5 fractions were considered. Equivalent doses were calculated for prostate (α/β= 1.5Gy), bladder and rectum (α/β= 3Gy).Results:The biological equivalent prostate dose was 86.2 and 92.9 Gyeq for the hypofractionation scenarios at 4.32 and 7.35 Gy/fx, respectively. The equivalent prostate D98 was degraded by on average 2.7 Gyeq for standard, and 3.1 and 4.0 Gyeq for the hypofractionated plans after accumulation. Differences between accumulated and planned Dmean/D2/EUD were generally reduced when reducing the number of fractions for bladder and rectum. The average Dmean/D2/EUD differences over all patients and organs‐at‐risk were 0.74/4.0/9.23, 0.49/3.64/5.51, 0.37/3.21/3.49 Gyeq for 44, 12 and 5 fractions.Conclusion:Hypofractionation makes proton therapy of prostate more susceptible to interfractional motion‐induced target dose degradation compared to the standard fractionation.

Clinical commissioning of an in vivo range verification system for prostate cancer treatment with anterior and anterior oblique proton beams

The purpose of this work is the clinical commissioning of a recently developed in vivo range verification system (IRVS) for treatment of prostate cancer by anterior and anterior oblique proton beams. The IRVS is designed to perform a complete workflow for pre-treatment range verification and adjustment. It contains specifically designed dosimetry and electronic hardware and a specific software for workflow control with database connection to the treatment and imaging systems. An essential part of the IRVS system is an array of Si-diode detectors, designed to be mounted to the endorectal water balloon routinely used for prostate immobilization. The diodes can measure dose rate as function of time from which the water equivalent path length (WEPL) and the dose received are extracted. The former is used for pre-treatment beam range verification and correction, if necessary, while the latter is to monitor the dose delivered to patient rectum during the treatment and serves as an additional verification. The entire IRVS workflow was tested for anterior and 30 degree inclined proton beam in both solid water and anthropomorphic pelvic phantoms, with the measured WEPL and rectal doses compared to the treatment plan. Gafchromic films were also used for measurement of the rectal dose and compared to IRVS results. The WEPL measurement accuracy was in the order of 1 mm and after beam range correction, the dose received by the rectal wall were 1.6% and 0.4% from treatment planning, respectively, for the anterior and anterior oblique field. We believe the implementation of IRVS would make the treatment of prostate with anterior proton beams more accurate and reliable.

Anteriorly Oriented Beam Arrangements with Daily in Vivo Range Verification for Proton Therapy of Prostate Cancer: Rectal Toxicity Rates.

To model whether in vivo range verification could reduce high-grade rectal toxicity for patients with prostate cancer treated with pencil beam scanning proton therapy by allowing novel proton beam arrangements compared to standard lateral opposed beams. Proton plans were generated for 8 patients with prostate cancer previously treated with photons by volumetric-modulated arc therapy (VMAT). The VMAT plans were generated by using a uniform 6-mm planning target volume (PTV) expansion. For the proton plans an additional distal margin (3.5% of beam range) was added to the uniform 6-mm PTV to account for range uncertainty, using 3 beam arrangements: (1) lateral opposed beams (LAT), (2) left and right anterior oblique beams (LAO/RAO), and (3) a single anterior-posterior beam (AP). Assuming use of in vivo range verification, plans were generated by using a reduced distal PTV and distal range uncertainty expansion (2 mm each) with AP (AP-2 mm) and LAO/RAO (LAO/RAO-2 mm) beam arrangements. Estimates of normal tissue complication probability (NTCP) for ≥grade 2 rectal bleeding were generated by using the Lyman-Kutcher-Burman model. Each proton and photon plan was able to achieve all prespecified rectal and bladder constraints. For the VMAT, LAT, AP, and LAO/RAO plans, estimated NTCP values for ≥grade 2 rectal bleeding were 0.19, 0.21, 0.24, and 0.2, respectively. For the AP-2 mm and LAO/RAO-2 mm plans, NTCP values were reduced to 0.11 and 0.1 with respect to ≥grade 2 rectal bleeding. Presuming that in vivo range verification for pencil beam scanning proton therapy could localize the distal falloff of the Bragg peak to within 2 mm, novel beam arrangements (AP and LAO/RAO) may reduce the risk of serious rectal bleeding, compared to VMAT and LAT proton treatment techniques. These are achieved without an increase in modeled bladder complication rates.

Protons for Prostate: Seeking Benefit via Anterior Beam Angles

For prostate treatments, robust evidence regarding the superiority of either IMRT or proton therapy is currently lacking. Some studies find that IMRT is better able to minimize high-dose regions in the bladder and rectal wall than standard bilateral proton beams, whilst others report the opposite. Here, we investigated whether a combination of anterior oblique (AO) beam angles, in vivo range verification, and state-of-the-art IMPT might substantially advance proton dose distributions relative to IMRT. The impact of uncertainty surrounding proton RBE was assessed. Eight patients were considered, all prescribed 79.2 Gy(E) to the prostate and 50.4 Gy(E) to the proximal 5-15 mm of seminal vesicles; IMRT and IMPT plans were created using MCO-based systems. The IMPT plans utilized AO beam angles (±35deg) with in-air spot sigma values of 12 mm at 60 MeV to 4.6 mm at 230MeV. Vowelized dose and LET distributions were simulated using Monte Carlo (TOPAS), and RBE was calculated according to three different models (Carabe 2012, Wedenberg 2013, McNamara 2015). The IMPT planning strategy (i) limited rectal toxicity with a 1 cm3 constraint of 81.58 Gy(E) and α/β = 3, and (ii) maximized dose to tumor to reduce under-dosage if true LET/RBE effects in vivo were lower than predicted. Table 1 shows that for all patients IMRT was able to adequately cover the CTV79.2 whilst meeting the rectal constraint. Typically, for AO IMPT it was not possible to find a plan that simultaneously met tumor and rectal constraints for fixed and variable RBE (vRBE) models, respectively. The tabulated vRBE data considers the median model.ePoster Abstracts 1144; Table 1Mean value across 8 patients (range)IMRTAO IMPT, RBE = 1.1AO IMPT, vRBE α/β = 3Dose received by 95% of CTV79.279.5 (79.3-79.8)77.8 (74.8-79.6)85.7 (82.7-87.5)Mean bladder dose16.4 (10.6-23.1)13.4 (7.5-18.7)14.1 (8.1-19.6)Mean penile bulb dose16.8 (8.8-25.1)14.2 (6.2-17.8)18.2 (8.6-22.4)Max rectal wall dose (1 cm3)79.6 (76.9-81.3)61.6 (60.7-63.8)81.4 (81.4-81.5) Open table in a new tab The question of whether improvements over IMRT can be gained using AO IMPT rests upon the validity of published LET/RBE models. If either the fixed RBE value of 1.1 or a vRBE model could be validated in vivo (via analysis of patient outcome data) then it would always be possible to use AO IMPT to dose-boost the prostate / improve normal tissue sparing relative to IMRT; however, simultaneously considering the two worst cases, fixed RBE for the tumor and vRBE for normal tissues, it is typically not possible to find an AO IMPT plan that meets both rectum and target constraints. This study 1) underlines the importance of resolving the question of proton RBE and 2) highlights that without further LET/RBE model validation, great care must be taken if AO proton fields are to be considered for prostate treatments.

TU-EF-304-05: Anterior Proton Beams for Prostate Treatments Lead to Substantial Elevations in Modeled RBE-Weighted Rectal Dose

Purpose: If a constant RBE of 1.1 is assumed, range-verified anterior oblique (AO) proton beams appear to offer the potential to reduce the mean dose delivered to the rectum, anterior rectal wall and penile bulb by a factor of ∼2 relative to standard bilateral (SB) proton beam arrangements. Additionally, AO proton beams targeted at the prostate avoid the femoral heads and so form a particularly appealing option for patients with hip prostheses. This study investigates LET enhancement at the distal edge of AO SOBPs, applying RBE models to consider the extent to which AO beams lead to hotspots in rectum biological dose. Methods: Eight patients were selected, all treated with passively scattered, SB proton beams to 79.2Gy(E) within the prostate and 50.4Gy(E) within the proximal 5–15mm of seminal vesicles. Additional plans utilizing AO beams (±35°) were created in XiO (Elekta) assuming a fixed RBE of 1.1. Voxelised dose and LET distributions were calculated using Monte Carlo (TOPAS). Three different LET/RBE models were applied (Carabe 2012, Wedenberg 2013, McNamara 2015). Results: Across the eight patients, the mean LET within the rectal wall was found to be 3.5(3.2–4.0)keV/µm for the SB plans compared to 10.5(8.6–13.0)keV/µm for the AO plans. Application of the median LET/RBE model to the AO plans, rather than a fixed RBE of 1.1, resulted in an increase of 13.6(11.9–14.7)GyRBE in maximum rectal wall (1cc) RBEw dose, leading to values of 90.4(90.0–91.3)GyRBE. Conclusion: relative to SB proton beams, AO proton beams exhibit substantially increased mean LET values within the rectal wall. For the passively scattered AO beams, modeling indicates that this enhancement is likely to translate into unacceptable RBEw dose hotspots. Whilst no RBE- LET model has yet been fully validated in-vivo, caution must be applied if AO beams are to be considered for prostate patients.

Intensity modulated proton therapy versus uniform scanning proton therapy: Treatment planning study of the prostate cancer in patients with a unilateral metallic hip prosthesis

The purpose of this study is to compare the dosimetric results between the uniform scanning proton therapy (USPT) and intensity modulated proton therapy (IMPT) plans for the prostate cancer in patients with a unilateral metallic hip prosthesis. Five prostate cancer cases with left (n = 3) and right (n = 2) metallic hip prostheses were included in this retrospective study. For each case, the USPT and IMPT plans were generated using two anterior-oblique beams and one lateral beam for a total dose of 79.2 Gy(RBE) to be delivered in 44 fractions. For a given case, the beam parameters, dose prescription, and delivery schema in the IMPT plan were kept identical to the ones in the USPT plan. The IMPT and USPT plans were compared for various dosimetric parameters. The mean dose to the target volume was comparable. Both the IMPT and USPT techniques achieved the target coverage goals. Dose homogeneity was found to be similar in the IMPT and USPT plans. For both the rectum and bladder, the IMPT plans produced favorable dosimetric results in the low-, medium-, and high-dose regions when compared to the USPT plans. For the high dose regions, the rectal V 70 was lower in the IMPT plans by about 3.89 cc when compared to the one in the USPT plans. The rectal V 80 in the IMPT plans (1.10 cc) was almost half than the one in the USPT plans (2.39 cc). In comparison to the USPT plans, the mean dose to the rectum, bladder, and femoral head were lower in the IMPT plans by about 8.91%, 4.15%, and 41.09%, respectively. Based on the preliminary results of five cases presented in this study, the IMPT plans provided slightly better dosimetric results compared to the USPT plans, especially in sparing the rectum and bladder in the low-, medium-, and high-dose regions, for the treatment of the prostate cancer in patients with a unilateral metallic hip prosthesis. Future studies need to address the impact of the setup uncertainties and intra-fraction prostate motion in the IMPT planning of the prostate cancer patients with prosthetic hip replacements.