Repurposing DailyQA3 for an efficient and spot position sensitive daily quality assurance tool for proton therapy.

INTRODUCTION: Daily quality assurance is an integral part of a radiotherapy workflow to ensure the dose is delivered safely and accurately to the patient. It is performed before the first treatment of the day and needs to be time and cost efficient for a multiple gantries proton center. In this study, we introduced an efficient method to perform QA for output constancy, range verification, spot positioning accuracy and imaging and proton beam isocenter coincidence with DailyQA3. METHODS: A stepped acrylic block of specific dimensions is fabricated and placed on top of the DailyQA3 device. Treatment plans comprising of two different spread-out Bragg peaks and five individual spots of 1.0 MU each are designed to be delivered to the device. A mathematical framework to measure the 2D distance between the detectors and individual spot is introduced and play an important role in realizing the spot positioning and centering QA. Lastly, a 5 months trends of the QA for two gantries are presented. RESULTS: The outputs are monitored by two ion chambers in the DailyQA3 and a tolerance of ± 3 % $ \pm 3\% $ are used. The range of the SOBPs are monitored by the ratio of ion chamber signals and a tolerance of ± 1 mm $ \pm 1\ {\mathrm{mm}}$ is used. Four diodes at ± 10 cm $ \pm 10\ {\mathrm{cm}}$ from the central ion chambers are used for spot positioning QA, while the central ion chamber is used for imaging and proton beam isocenter coincidence QA. Using the framework, we determined the absolute signal threshold corresponding to the offset tolerance between the individual proton spot and the detector. A 1.5 mm $1.5\ {\mathrm{mm}}$ tolerances are used for both the positioning and centering QA. No violation of the tolerances is observed in the 5 months trends for both gantries. CONCLUSION: With the proposed approach, we can perform four QA items in the TG224 within 10 min.

Commissioning and clinical implementation of an independent dose calculation system for scanned proton beams.

PURPOSE: Experimental patient-specific QA (PSQA) is a time and resource-intensive process, with a poor sensitivity in detecting errors. Radiation therapy facilities aim to substitute it by means of independent dose calculation (IDC) in combination with a comprehensive beam delivery QA program. This paper reports on the commissioning of the IDC software tool myQA iON (IBA Dosimetry) for proton therapy and its clinical implementation at the MedAustron Ion Therapy Center. METHODS: The IDC commissioning work included the validation of the beam model, the implementation and validation of clinical CT protocols, and the evaluation of patient treatment data. Dose difference maps, gamma index distributions, and pass rates (GPR) have been reviewed. The performance of the IDC tool has been assessed and clinical workflows, simulation settings, and GPR tolerances have been defined. RESULTS: Beam model validation showed agreement of ranges within ± 0.2 mm, Bragg-Peak widths within ± 0.1 mm, and spot sizes at various air gaps within ± 5% compared to physical measurements. Simulated dose in 2D reference fields deviated by -0.3% ± 0.5%, while 3D dose distributions differed by 1.8% on average to measurements. Validation of the CT calibration resulted in systematic differences of 2.0% between IDC and experimental data for tissue like samples. GPRs of 99.4 ± 0.6% were found for head, head and neck, and pediatric CT protocols on a 2%/2 mm gamma criterion. GPRs for the adult abdomen protocol were at 98.9% on average with 3%/3 mm. Root causes of GPR outliers, for example, implants were identified and evaluated. CONCLUSION: IDC has been successfully commissioned and integrated into the MedAustron clinical workflow for protons in 2021. IDC has been stepwise and safely substituting experimental PSQA since February 2021. The initial reduction of proton experimental PSQA was about 25% and reached up to 90% after 1 year.

Optimal minimum MU for intensity-modulated proton therapy with pencil-beam scanning proton beams.

PURPOSE: A higher minimum monitor unit (minMU) for pencil-beam scanning proton beams in intensity-modulated proton therapy is preferred for more efficient delivery. However, plan quality may be compromised when the minMU is too large. This study aimed to identify the optimal minMU (OminMU) to improve plan delivery efficiency while maintaining high plan quality. METHODS: We utilized clinical plans including six anatomic sites (brain, head and neck, breast, lung, abdomen, and prostate) from 23 patients previously treated with the Varian ProBeam system. The minMU of each plan was increased from the current clinical minMU of 1.1 to 3-24 MU depending on the daily prescribed dose (DPD). The dosimetric parameters of the plans were evaluated for consistency against a 1.1-minMU plan for target coverage as well as organs-at-risk dose sparing. DPD/minMU was defined as the ratio of DPD to minMU (cGy/MU) to find the OminMU by ensuring that dosimetric parameters did not differ by >1% compared to those of the 1.1-minMU plan. RESULTS: All plans up to 5 minMU showed no significant dose differences compared to the 1.1-minMU plan. Plan qualities remained acceptable when DPD/minMU ≥35 cGy/MU. This suggests that the 35 cGy/MU criterion can be used as the OminMU, which implies that 5 MU is the OminMU for a conventional fraction dose of 180 cGy. Treatment times were decreased by an average of 32% (max 56%, min 7%) and by an average of 1.6 min when the minMU was increased from 1.1 to OminMU. CONCLUSION: A clinical guideline for OminMU has been established. The minMU can be increased by 1 MU for every 35 cGy of DPD without compromising plan quality for most cases analyzed in this study. Significant treatment time reduction of up to 56% was observed when the suggested OminMU is used.

Fetal dose assessment in a pregnant patient with brain tumor: A comparative study of proton PBS and 3DCRT/VMAT radiation therapy techniques.

PURPOSE: The treatment of brain tumors in pregnant patients poses challenges, as the out-of-field dose exposure to the fetus can potentially be harmful. A pregnant patient with prior radiation treatment was presented with a brain tumor at our clinic. This work reports on our pre-treatment study that compared fetal dose exposure between intensity-modulated proton therapy (IMPT) using pencil beam scanning (PBS) and conventional photon 3D conformal radiation therapy (3DCRT) and volumetric-modulated arc therapy (VMAT), and the subsequent pregnant patient's radiation treatment. MATERIALS AND METHODS: Pre-treatment measurements of clinical plans, 3DCRT, VMAT, and IMPT, were conducted on a phantom. Measurements were performed using a device capable of neutron detections, closely following AAPM guidelines, TG158. For photon measurements, fetus shielding was utilized. On patient treatment days, which was determined to be proton treatment, shielding was used only during daily imaging for patient setup. Additionally, an in vivo measurement was conducted on the patient. RESULTS: Measurements showed that IMPT delivered the lowest fetal dose, considering both photon and neutron out-of-field doses to the fetus, even when shielding was implemented for photon measurements. Additionally, the proton plans demonstrated superior treatment for the mother, a reirradiation case. CONCLUSION: The patient was treated with proton therapy, and the baby was subsequently delivered at full term with no complications. This case study supports previous clinical findings and advocates for the expanded use of proton therapy in this patient population.

Carbon ion radiotherapy with pencil beam scanning for hepatocellular carcinoma: Long-term outcomes from a phase I trial.

This study evaluates the feasibility of the pencil beam scanning technique of carbon ion radiotherapy (CIRT) in the setting of hepatocellular carcinoma (HCC) and establishes the maximum tolerated dose (MTD) calculated by the Local Effect Model version I (LEM-I) with a dose escalation plan. The escalated relative biological effectiveness-weighted dose levels included 55, 60, 65, and 70 Gy in 10 fractions. Active motion management techniques were employed, and several measures were applied to mitigate the interplay effect induced by a moving target. CIRT was planned with the LEM-I-based treatment planning system and delivered by raster scanning. Offline PET/CT imaging was used to verify the beam range. Offline adaptive replanning was performed whenever required. Twenty-three patients with a median tumor size of 4.3 cm (range, 1.7-8.5 cm) were enrolled in the present study. The median follow-up time was 56.1 months (range, 5.7-74.4 months). No dose limiting toxicity was observed until 70 Gy, and MTD had not been reached. No patients experienced radiation-induced liver disease within 6 months after the completion of CIRT. The overall survival rates at 1, 3, and 5 years were 91.3%, 81.9%, and 67.1% after CIRT, respectively. The local progression-free survival and progression-free survival rates at 1, 3 and 5 years were 100%, 94.4%, and 94.4% and 73.6%, 59.2%, and 37.0%, respectively. The raster scanning technique could be used to treat HCC. However, caution should be exercised to mitigate the interplay effect. CIRT up to 70 Gy in 10 fractions over 2 weeks was safe and effective for HCC.

Early outcome after craniospinal irradiation with pencil beam scanning proton therapy for children, adolescents and young adults with brain tumors.

Central nervous system (CNS) tumors are the most common solid malignancies in children and adolescents and young adults (C-AYAs). Craniospinal irradiation (CSI) is an essential treatment component for some malignancies, but it can also lead to important toxicity. Pencil beam scanning proton therapy (PBSPT) allows for a minimization of dose delivered to organs at risk and, thus, potentially reduced acute and late toxicity. This study aims to report the clinical outcomes and toxicity rates after CSI for C-AYAs treated with PBSPT. Seventy-one C-AYAs (median age: 7.4 years) with CNS tumors were treated with CSI between 2004 and 2021. Medulloblastoma (n = 42: 59%) and ependymoma (n = 8; 11%) were the most common histologies. Median prescribed total PBSPT dose was 54 GyRBE (range: 18-60.4), and median prescribed craniospinal dose was 24 GyRBE (range: 18-36.8). Acute and late toxicities were coded according to Common Terminology Criteria for Adverse Events. After a median follow-up of 24.5 months, the estimated 2-year local control, distant control, and overall survival were 86.3%, 80.5%, and 84.7%, respectively. Late grade ≥3 toxicity-free rate was 92.6% at 2 years. Recurrent and metastatic tumors were associated with worse outcome. In conclusion, excellent tumor control with low toxicity rates was observed in C-AYAs with brain tumors treated with CSI using PBSPT.

Acute genitourinary toxicity of pencil beam scanning proton therapy for localized prostate cancer: utility of the transition zone index and average urinary flow rate in predicting acute urinary retention.

BACKGROUND: The purpose of this study was to evaluate the incidence of acute genitourinary toxicities in patients undergoing pencil beam scanning proton therapy for prostate cancer and investigate predictive factors associated with acute urinary retention. METHODS: A total of 227 patients treated between 2018 and 2021 were divided into the normo-fractionated proton therapy group (n = 107) and the moderately hypo-fractionated proton therapy group (n = 120), with prescribed doses of 76-78 Gy relative biological effectiveness in 38-39 fractions and 60-63 Gy relative biological effectiveness in 20-21 fractions, respectively. Uroflowmetry parameters and the transition zone index were prospectively evaluated. RESULTS: Forty-five patients (42%) in the normo-fractionated proton therapy and 33 (28%) in the moderately hypo-fractionated proton therapy developed acute grade 2 genitourinary toxicities (P = 0.02). The most common acute genitourinary toxicity was acute urinary retention. Thirty-nine patients (36%) treated with normo-fractionated proton therapy and 27 (23%) treated with moderately hypo-fractionated proton therapy developed grade 2 acute urinary retention (P = 0.02). No patients developed grade ≥ 3 toxicity. Univariate analysis showed the transition zone index, prostate volume, international prostate symptom score, voided volume, maximum flow rate and average flow rate were associated with grade 2 acute urinary retention. Multivariate analysis in both groups revealed the transition zone index (P = 0.025 and 0.029) and average flow rate (P = 0.039 and 0.044) were predictors of grade 2 acute urinary retention. CONCLUSIONS: The incidence of acute genitourinary toxicities was lower in the moderately hypo-fractionated proton therapy compared with the normo-fractionated proton therapy. Lower pretreatment average flow rate and a higher transition zone index were useful predictors of grade 2 acute urinary retention.

Is it beneficial to use apertures in proton radiosurgery with a scanning beam? A dosimetric comparison in neurinoma and meningioma patients.

PURPOSE: To assess the dosimetric advantages of apertures in intracranial single fraction proton radiosurgery. MATERIALS AND METHODS: Six neuroma and 10 meningioma patients were investigated. For each patient, six plans were computed, with two spot spacing and three aperture settings (no apertures, 5 and 8 mm margin between aperture and clinical target volume [CTV]). All plans were optimized on the CTV with the same beam arrangement and the same single-field robust optimization (2 mm setup errors, 3.5% range uncertainties). Robustness analysis was performed with 0.5 and 1.0 mm systematic setup errors and 3.5% range uncertainties. CTV coverage in the perturbed scenarios and healthy brain tissue sparing in the surrounding of the CTV were compared. RESULTS: Meningiomas were larger and at a shallow depth than neuromas. In neuromas, spot spacing did not affect OAR doses or the robustness of CTV coverage and the apertures reduced brain dose without any significant impact on CTV robustness. In meningiomas, smaller spot spacing produced a reduction in brain V5Gy and improved robustness of CTV coverage; in addition, an 8 mm margin aperture reduced low and medium brain tissue doses without affecting robustness in the 0.5 mm perturbed scenario. A 5 mm margin aperture caused a reduction of plan robustness. CONCLUSION: The optimal use of apertures is a trade-off between sparing of low and medium dose to the healthy brain and robustness of target coverage, also depending on size and depth of the lesion.

Small spot size versus large spot size: Effect on plan quality for lung cancer in pencil beam scanning proton therapy.

PURPOSE: The purpose of the current study was to evaluate the impact of spot size on the interplay effect, plan robustness, and dose to the organs at risk for lung cancer plans in pencil beam scanning (PBS) proton therapy METHODS: The current retrospective study included 13 lung cancer patients. For each patient, small spot (∼3 mm) plans and large spot (∼8 mm) plans were generated. The Monte Carlo algorithm was used for both robust plan optimization and final dose calculations. Each plan was normalized, such that 99% of the clinical target volume (CTV) received 99% of the prescription dose. Interplay effect was evaluated for treatment delivery starting in two different breathing phases (T0 and T50). Plan robustness was investigated for 12 perturbed scenarios, which combined the isocenter shift and range uncertainty. The nominal and worst-case scenario (WCS) results were recorded for each treatment plan. Equivalent uniform dose (EUD) and normal tissue complication probability (NTCP) were evaluated for the total lung, heart, and esophagus. RESULTS: In comparison to large spot plans, the WCS values of small spot plans at CTV D95% , D96% , D97% , D98% , and D99% were higher with the average differences of 2.2% (range, 0.3%-3.7%), 2.3% (range, 0.5%-4.0%), 2.6% (range, 0.6%-4.4%), 2.7% (range, 0.9%-5.2%), and 2.7% (range, 0.3%-6.0%), respectively. The nominal and WCS mean dose and EUD for the esophagus, heart, and total lung were higher in large spot plans. The difference in NTCP between large spot and small spot plans was up to 1.9% for the total lung, up to 0.3% for the heart, and up to 32.8% for the esophagus. For robustness acceptance criteria of CTV D95% ≥ 98% of the prescription dose, seven small spot plans had all 12 perturbed scenarios meeting the criteria, whereas, for 13 large spot plans, there were ≥2 scenarios failing to meet the criteria. Interplay results showed that, on average, the target coverage in large spot plans was higher by 1.5% and 0.4% in non-volumetric and volumetric repainting plans, respectively. CONCLUSION: For robustly optimized PBS lung cancer plans in our study, a small spot machine resulted in a more robust CTV against the setup and range errors when compared to a large spot machine. In the absence of volumetric repainting, large spot PBS lung plans were more robust against the interplay effect. The use of a volumetric repainting technique in both small and large spot PBS lung plans led to comparable interplay target coverage.

Validation of pencil beam scanning proton therapy with multi-leaf collimator calculated by a commercial Monte Carlo dose engine.

This study aimed to evaluate the clinical beam commissioning results and lateral penumbra characteristics of our new pencil beam scanning (PBS) proton therapy using a multi-leaf collimator (MLC) calculated by use of a commercial Monte Carlo dose engine. Eighteen collimated uniform dose plans for cubic targets were optimized by the RayStation 9A treatment planning system (TPS), varying scan area, modulation widths, measurement depths, and collimator angles. To test the patient-specific measurements, we also created and verified five clinically realistic PBS plans with the MLC, such as the liver, prostate, base-of-skull, C-shape, and head-and-neck. The verification measurements consist of the depth dose (DD), lateral profile (LP), and absolute dose (AD). We compared the LPs and ADs between the calculation and measurements. For the cubic plans, the gamma index pass rates (γ-passing) were on average 96.5% ± 4.0% at 3%/3 mm for the DD and 95.2% ± 7.6% at 2%/2 mm for the LP. In several LP measurements less than 75 mm depths, the γ-passing deteriorated (increased the measured doses) by less than 90% with the scattering such as the MLC edge and range shifter. The deteriorated γ-passing was satisfied by more than 90% at 2%/2 mm using uncollimated beams instead of collimated beams except for three planes. The AD differences and the lateral penumbra width (80%-20% distance) were within ±1.9% and ± 1.1 mm, respectively. For the clinical plan measurements, the γ-passing of LP at 2%/2 mm and the AD differences were 97.7% ± 4.2% on average and within ±1.8%, respectively. The measurements were in good agreement with the calculations of both the cubic and clinical plans inserted in the MLC except for LPs less than 75 mm regions of some cubic and clinical plans. The calculation errors in collimated beams can be mitigated by substituting uncollimated beams.

Proton pencil-beam scanning radiotherapy in the treatment of nasopharyngeal cancer: dosimetric parameters and 2-year results.

OBJECTIVES:  Patients with nasopharyngeal cancer are candidates for proton radiotherapy due to large and comprehensive target volumes, and the necessity for sparing of healthy tissues. The aim of this work is to evaluate treatment outcome and toxicity profile of patients treated with proton pencil-beam scanning radiotherapy. MATERIALS AND METHODS:  Between Jan 2013 and June 2018, 40 patients were treated for nasopharyngeal cancer (NPC) with IMPT (proton radiotherapy with modulated intensity). Median age was 47 years and the majority of patients had locally advanced tumors (stage 2-8 patients. (20%); stage 3-18 patients (45%); stage 4A-10 patients. (25%); stage 4B-4 patients. (10%). Median of total dose was 74 GyE (70-76 GyE) in 37 fractions (35-38). Bilateral neck irradiation was used in all cases. Concomitant chemotherapy was applied in 34 cases. (85%). Median follow-up time was 24 (1.5-62) months. RESULTS: Two-year overall survival (OS), disease-free survival (DFS), and local control (LC) were 80%, 75%, and 84%, respectively. Acute toxicity was generally mild despite large target volumes and concurrent application of chemotherapy with skin toxicity and dysphagia reported as the most frequent acute side effects. The insertion of a percutaneous endoscopic gastrectomy (PEG) was necessary in four cases (10%). Serious late toxicity (G > 3. RTOG) was observed in two patients (5%) (dysphagia and brain necrosis). CONCLUSION:  IMPT for nasopharyngeal cancer patients is feasible with mild acute toxicity. Treatment outcomes are promising despite the high percentage of advanced disease in this group.

Using patient-specific bolus for pencil beam scanning proton treatment of periorbital disease.

PURPOSE: A unique mantle cell lymphoma case with bilateral periorbital disease unresponsive to chemotherapy and with dosimetry not conducive to electron therapy was treated with pencil beam scanning (PBS) proton therapy. This patient presented treatment planning challenges due to the thin target, immediately adjacent organs at risk (OAR), and nonconformal orbital surface anatomy. Therefore, we developed a patient-specific bolus and hypothesized that it would provide superior setup robustness, dose uniformity and dose conformity. MATERIALS/METHODS: A blue-wax patient-specific bolus was generated from the patient's face contour to conform to his face and eliminate air gaps. A relative stopping power ratio (RSP) of 0.972 was measured for the blue-wax, and the HUs were overridden accordingly in the treatment planning system (TPS). Orthogonal kV images were used for bony alignment and then to ensure positioning of the bolus through fiducial markers attached to the bolus and their contours in TPS. Daily CBCT was used to confirm the position of the bolus in relation to the patient's surface. Dosimetric characteristics were compared between (a) nonbolus, (b) conventional gel bolus and (c) patient-specific bolus plans. An in-house developed workflow for assessment of daily treatment dose based on CBCT images was used to evaluate inter-fraction dose accumulation. RESULTS: The patient was treated to 24 cobalt gray equivalent (CGE) in 2 CGE daily fractions to the bilateral periorbital skin, constraining at least 50% of each lacrimal gland to under 20 Gy. The bolus increased proton beam range by adding 2-3 energy layers of different fields to help achieve better dose uniformity and adequate dose coverage. In contrast to the plan with conventional gel bolus, dose uniformity was significantly improved with patient-specific bolus. The global maximum dose was reduced by 7% (from 116% to 109%). The max and mean doses were reduced by 6.0% and 7.7%, respectively, for bilateral retinas, and 3.0% and 13.9% for bilateral lacrimal glands. The max dose of the lens was reduced by 2.1%. The rigid shape, along with lightweight, and smooth fit to the patient face was well tolerated and reported as "very comfortable" by the patient. The daily position accuracy of the bolus was within 1 mm based on IGRT marker alignment. The daily dose accumulation indicates that the target coverage and OAR doses were highly consistent with the planning intention. CONCLUSION: Our patient-specific blue-wax bolus significantly increased dose uniformity, reduced OAR doses, and maintained consistent setup accuracy compared to conventional bolus. Quality PBS proton treatment for periorbital tumors and similar challenging thin and shallow targets can be achieved using such patient-specific bolus with robustness on both setup and dosimetry.

Investigating volumetric repainting to mitigate interplay effect on 4D robustly optimized lung cancer plans in pencil beam scanning proton therapy.

PURPOSE: The interplay effect between dynamic pencil proton beams and motion of the lung tumor presents a challenge in treating lung cancer patients in pencil beam scanning (PBS) proton therapy. The main purpose of the current study was to investigate the interplay effect on the volumetric repainting lung plans with beam delivery in alternating order ("down" and "up" directions), and explore the number of volumetric repaintings needed to achieve acceptable lung cancer PBS proton plan. METHOD: The current retrospective study included ten lung cancer patients. The total dose prescription to the clinical target volume (CTV) was 70 Gy(RBE) with a fractional dose of 2 Gy(RBE). All treatment plans were robustly optimized on all ten phases in the 4DCT data set. The Monte Carlo algorithm was used for the 4D robust optimization, as well as for the final dose calculation. The interplay effect was evaluated for both the nominal (i.e., without repainting) as well as volumetric repainting plans. The interplay evaluation was carried out for each of the ten different phases as the starting phases. Several dosimetric metrics were included to evaluate the worst-case scenario (WCS) and bandwidth based on the results obtained from treatment delivery starting in ten different breathing phases. RESULTS: The number of repaintings needed to meet the criteria 1 (CR1) of target coverage (D95%  ≥ 98% and D99%  ≥ 97%) ranged from 2 to 10. The number of repaintings needed to meet the CR1 of maximum dose (ΔD1%  < 1.5%) ranged from 2 to 7. Similarly, the number of repaintings needed to meet CR1 of homogeneity index (ΔHI < 0.03) ranged from 3 to 10. For the target coverage region, the number of repaintings needed to meet CR1 of bandwidth (<100 cGy) ranged from 3 to 10, whereas for the high-dose region, the number of repaintings needed to meet CR1 of bandwidth (<100 cGy) ranged from 1 to 7. Based on the overall plan evaluation criteria proposed in the current study, acceptable plans were achieved for nine patients, whereas one patient had acceptable plan with a minor deviation. CONCLUSION: The number of repaintings required to mitigate the interplay effect in PBS lung cancer (tumor motion < 15 mm) was found to be highly patient dependent. For the volumetric repainting with an alternating order, a patient-specific interplay evaluation strategy must be adopted. Determining the optimal number of repaintings based on the bandwidth and WCS approach could mitigate the interplay effect in PBS lung cancer treatment.

Assessment of the Relative Biological Efficiency of Pencil Beam Scanning of Protons in Mice in Vivo.

The effect of proton pencil beam scanning in the dose range of 4.5-15 Gy on the radiosensitivity of mice under irradiation in two regions of the Bragg curve was studied according to the criteria of 30-day survival, dynamics of death, and average lifespan of mice. The relative biological effectiveness (RBE) value of protons relative to X-ray radiation before and at the Bragg peak determined by the LD50/30 index was 0.86 and 0.94, respectively, and by the criterion of 30-day survival at a dose of 6.5 Gy it was 0.83 and 0.84, respectively. With similar RBE values for protons in different regions of the Bragg curve, significant differences in the dynamics of the course of radiation sickness were revealed, which indicates different damage to critical systems and organs of animals and the induction of compensatory mechanisms involved in the formation of stress responses at the organismal level.

Combined Effect of Neutron and Proton Radiations on the Growth of Solid Ehrlich Ascites Carcinoma and Remote Effects in Mice.

The combined effect of the irradiation with a proton pencil scanning beam (PBS) at a total dose of 80 Gy and neutron radiation at a dose of 5 Gy on the growth of solid Ehrlich ascites carcinoma (EAC) and the remote effects in tumor-bearing mice was studied. Combined irradiation of mice with neutrons before and after irradiation with PBS, as well as irradiation only with PBS, effectively suppressed the growth of solid EAC within 1 month. In terms of the frequency and severity of radiation-induced skin reactions of mice observed 15-40 days after therapy, neutron irradiation after the irradiation with PBS showed better values of these parameters as compared to only PBS; however, exposure to neutrons before PBS was more damaging as compared to the other two options. It was also shown that the tumor relapse rate in the groups of animals with combined irradiation was higher, and the total lifespan was lower than the group of mice irradiated with PBS alone.

Clinical outcomes and quality of life in children and adolescents with primary brain tumors treated with pencil beam scanning proton therapy.

BACKGROUND: Long-term treatment-related toxicity may substantially impact well-being, quality of life (QoL), and health of children/adolescents with brain tumors (CBTs). Strategies to reduce toxicity include pencil beam scanning (PBS) proton therapy (PT). This study aims to report clinical outcomes and QoL in PBS-treated CBTs. PROCEDURE: We retrospectively reviewed 221 PBS-treated CBTs aged <18 years. Overall-free (OS), disease-free (DFS), and late-toxicity-free survivals (TFS), local control (LC) and distant (DC) brain/spinal control were calculated using Kaplan-Meier estimates. Prospective QoL reports from 206 patients (proxies only ≤4 years old [yo], proxies and patients ≥5 yo) were descriptively analyzed. Median follow-up was 51 months (range, 4-222). RESULTS: Median age at diagnosis was 3.1 years (range, 0.3-17.7). The main histologies were ependymoma (n = 88; 39.8%), glioma (n = 37; 16.7%), craniopharyngioma (n = 22; 10.0%), atypical teratoid/rhabdoid tumor (ATRT) (n = 21; 9.5%) and medulloblastoma (n = 15; 6.8%). One hundred sixty (72.4%) patients received chemotherapy. Median PT dose was 54 Gy(relative biological effectiveness) (range, 18.0-64.8). The 5-year OS, DFS, LC, and DC (95% CI) were 79.9% (74-85.8), 65.2% (59.8-70.6), 72.1% (65.4-78.8), and 81.8% (76.3-87.3), respectively. Late PT-related ≥G3 toxicity occurred in 19 (8.6%) patients. The 5-year ≥G3 TFS was 91.0% (86.3-95.7). Three (1.4%) secondary malignancies were observed. Patients aged ≤3 years at PT (P = .044) or receiving chemotherapy (P = .043) experienced more ≥G3 toxicity. ATRT histology independently predicted distant brain failure (P = .046) and death (P = .01). Patients aged ≥5 years self-rated QoL higher than their parents (proxy assessment). Both reported lower social functioning and cognition after PT than at baseline, but near-normal long-term global well-being. QoL was well below normal before and after PT in children ≤4 years. CONCLUSIONS: The outcome of CBTs was excellent after PBS. Few patients had late ≥G3 toxicity. Patients aged <5 years showed worse QoL and toxicity outcomes.

Outcomes of adolescents and young adults treated for brain and skull base tumors with pencil beam scanning proton therapy.

BACKGROUND: The use of proton therapy (PT) in adolescents and young adults (AYAs) is becoming increasingly popular. This study aims to assess the outcomes and late toxicity consequences in AYAs (15-39 years) with brain/skull base tumors treated with pencil beam scanning proton therapy. METHODS: One hundred seventy six AYAs treated curatively at the Paul Scherrer Institute (PSI) were identified. Median age was 30 years (range 15-39) and median prescribed dose was 70.0 Gy (relative biological effectiveness [RBE]) (range 50.4-76.0). The most common tumors treated were chordomas/chondrosarcomas (61.4%), followed by gliomas (15.3%), and meningiomas (14.2%). RESULTS: After a median follow up of 66 months (range 12-236), 24 (13.6%) local only failures and one (0.6%) central nervous system (CNS) distant only failure were observed. The 6-year local control, distant progression-free survival, and overall survival were 83.2%, 97.4%, and 90.2%, respectively. The 6-year high-grade (≥grade [G] 3) PT-related late toxicity-free survival was 88.5%. Crude late toxicity rates were 26.2% G1, 37.8% G2, 12.2% G3, 0.6% G4, and 0.6% G5. The one G4 toxicity was a retinopathy and one G5 toxicity was a brainstem hemorrhage. The 6-year cumulative incidences for any late PT-related pituitary, ototoxicity, and neurotoxicity were 36.3%, 18.3%, and 25.6%; whilst high-grade (≥G3) ototoxicity and neurotoxicity were 3.4% and 2.9%, respectively. No secondary malignancies were observed. The rate of unemployment was 9.5% pre-PT, increasing to 23.8% post-PT. Sixty-two percent of survivors were working whilst 12.7% were in education post-PT. CONCLUSIONS: PT is an effective treatment for brain/skull base tumors in the AYA population with a reasonable late toxicity profile. Despite good clinical outcomes, around one in four AYA survivors are unemployed after treatment.

Beam characteristics of the first clinical 360° rotational single gantry room scanning pencil beam proton treatment system and comparisons against a multi-room system.

PURPOSE: The purpose of this study was to present the proton beam characteristics of the first clinical single-room ProBeam Compact™ proton therapy system (SRPT) and comparison against multi-room ProBeam™ system (MRPT). MATERIALS AND METHODS: A newly designed SRPT with proton beam energies ranging from 70 to 220 MeV was commissioned in late 2019. Integrated depth doses (IDDs) were scanned using 81.6 mm diameter Bragg peak chambers and normalized by outputs at 15 mm WET and 1.1 RBE offset, following the methodology of TRS 398. The in-air beam spot profiles were acquired by a planar scintillation device, respectively, at ISO, upper and down streams, fitted with single Gaussian distribution for beam modeling in Eclipse v15.6. The field size effect was adjusted for the best overall accuracy of clinically relevant field QAs. The halo effects at near surface were quantified by a pinpoint ionization chamber. Its major dosimetric characteristics were compared against MRPT comparable beam dataset. RESULTS: Contrast to MRPT, an increased proton straggling in the Bragg peak region was found with widened beam distal falloffs and elevated proximal transmission dose values. Integrated depth doses showed 0.105-0.221 MeV (energy sigma) or 0.30-0.94 mm broader Bragg peak widths (Rb80 -Ra80 ) for 130 MeV or higher energy beams and up to 0.48-0.79 mm extended distal falloffs (Rb20 -Rb80 ). Minor differences were identified in beam spot sizes, spot divergences, proton particles/MU, and field size output effects. High passing scores are reported for independent end-to-end dosimetry checks by IROC and for initial 108 field-specific QAs at 3%/3 mm Gamma index with fields regardless with or without range shifters. CONCLUSIONS: The author highlighted the dosimetry differences in IDDs mainly caused by the shortened beam transport system of SRPT, for which new acceptance criteria were adapted. This report offers a unique reference for future commissioning, beam modeling, planning, and analysis of QA and clinical studies.

Impact of magnetic field regulation in conjunction with the volumetric repainting technique on the spot positions and beam range in pencil beam scanning proton therapy.

PURPOSE: The objective of this study was to evaluate the impact of the magnetic field regulation in conjunction with the volumetric repainting technique on the spot positions and range in pencil beam scanning proton therapy. METHODS: "Field regulation" - a feature to reduce the switching time between layers by applying a magnetic field setpoint (instead of a current setpoint) has been implemented on the proton beam delivery system at the Miami Cancer Institute. To investigate the impact of field regulation for the volumetric repainting technique, several spot maps were generated with beam delivery sequence in both directions, that is, irradiating from the deepest layer to the most proximal layer ("down" direction) as well as irradiating from the most proximal layer to the deepest layer ("up" direction). Range measurements were performed using a multi-layer ionization chamber array. Spot positions were measured using two-dimensional and three-dimensional scintillation detectors. For range and central-axis spot position, spot maps were delivered for energies ranging from 70-225 MeV. For off-axis spot positions, the maps were delivered for high-, medium, and low-energies at eight different gantry angles. The results were then compared between the "up" and "down" directions. RESULTS: The average difference in range for given energy between "up" and "down" directions was 0.0 ± 0.1 mm. The off-axis spot position results showed that 846/864 of the spots were within ±1 mm, and all off-axis spot positions were within ±1.2 mm. For spots (n = 126) at the isocenter, the evaluation between "up" and "down" directions for given energy showed the spot position difference within ±0.25 mm. At the nozzle entrance, the average differences in X and Y positions for given energy were 0.0 ± 0.2 mm and -0.0 ± 0.4 mm, respectively. At the nozzle exit, the average differences in X and Y positions for given energy were 0.0 ± 0.1 mm and -0.1 ± 0.1 mm, respectively. CONCLUSION: The volumetric repainting technique in magnetic field regulation mode resulted in acceptable spot position and range differences for our beam delivery system. The range differences were found to be within ±1 mm (TG224). For the spot positions (TG224: ±1 mm), the central axis measurements were within ±1 mm, whereas for the off-axis measurements, 97.9% of the spots were within ±1 mm, and all spots were within ±1.2 mm.

Measurement-based study on characterizing symmetric and asymmetric respiratory motion interplay effect on target dose distribution in the proton pencil beam scanning.

Pencil beam scanning proton therapy makes possible intensity modulation, resulting in improved target dose conformity and organ-at-risk (OAR) dose sparing. This benefit, however, results in increased sensitivity to certain clinical and beam delivery parameters, such as respiratory motion. These effects can cause plan degeneration, which could lead to decreased tumor dose or increased OAR dose. This study evaluated the measurements of proton pencil beam scanning delivery made with a 2D ion chamber array in solid water on a 1D motion platform, where respiratory motion was simulated using sine and cosine4 waves representing sinusoidal symmetric and realistic asymmetric breathing motions, respectively. Motion amplitudes were 0.5 cm and 1 cm corresponding to 1 cm and 2 cm of maximum respiratory excursions, respectively, with 5 sec fixed breathing cycle. The treatment plans were created to mimic spherical targets of 3 cm or 10 cm diameter located at 5 cm or 1 cm depth in solid water phantom. A reference RBE dose of 200 cGy per fraction was delivered in 1, 5, 10, and 15 fractions for each dataset. We evaluated dose conformity and uniformity at the center plane of targets by using the Conformation Number and the Homogeneity Index, respectively. Results indicated that dose conformity as well as homogeneity was more affected by motion for smaller targets. Dose conformity was better achieved for symmetric breathing patterns than asymmetric breathing patterns regardless of the number of fractions. The presence of a range shifter with shallow targets reduced the motion effect by improving dose homogeneity. While motion effects are known to be averaged out over the course of multifractional treatments, this might not be true for proton pencil beam scanning under asymmetrical breathing pattern.