Beam Scanning Proton Research Articles

Is noncoplanar plan more robust to inter-fractional variations than coplanar plan in treating bilateral HN tumors with pencil-beam scanning proton beams?

Noncoplanar plans (NCPs) are commonly used for proton treatment of bilateral head and neck (HN) malignancies. NCP requires additional verification setup imaging between beams to correct residual errors of robotic couch motion, which increases imaging dose and total treatment time. This study compared the quality and robustness of NCPs with those of coplanar plans (CPs). Under an IRB-approved study, CPs were created retrospectively for 10 bilateral HN patients previously treated with NCPs maintaining identical beam geometry of the original plan but excluding couch rotations. Plan robustness to the inter-fractional variation (IV) of both plans was evaluated through the Dose Volume Histograms (DVH) of weekly quality assurance CT (QACT) sets (39 total). In addition, delivery efficiency for both plans was compared using total treatment time (TTT) and beam-on time (BOT). No significant differences in plan quality were observed in terms of clinical target volume (CTV) coverage (D95) or organ-at-risk (OAR) doses (p>0.4 for all CTVs and OARs). No significant advantage of NCPs in the robustness to IV was found over CP, either. Changes in D95 of QA plans showed a linear correlation (slope=1.006, R2 >0.99) between NCP and CP for three CTV data points (CTV1, CTV2, and CTV3) in each QA plan (117 data points for 39 QA plans). NCPs showed significantly higher beam delivery time than CPs for TTT (539±50vs. 897±142s; p<0.001); however, no significant differences were observed for BOT. NCPs are not more robust to IV than CPs when treating bilateral HN tumors with pencil-beam scanning proton beams. CPs showed plan quality and robustness similar to NCPs while reduced treatment time (∼6min). This suggests that CPs may be a more efficient planning technique for bilateral HN cancer proton therapy.

CT-on-Rails Utilization for Image Guidance and Plan Adaptation at a Single-Room Proton Therapy Center.

In-room CT-on-rails is a relatively rare imaging modality in proton therapy. This work evaluated the utilization of CT-on-rails (CTOR) for image guidance and plan adaptation at a single-room proton therapy center. All patients treated from the proton center beginning treatment to the current date were evaluated (May 2021 - January 2023). Patients were treated using a Mevion S250i scanning beam proton therapy system with an in-room Definition Edge CTOR. The image guidance technique utilized for each patient was evaluated (CTOR, orthogonal planar kV imaging, or both). For patients who required a new CT for plan adaptation, the use of CT images from CTOR or a new simulation CT was assessed. Of the 132 patients treated over the evaluated time period, 56.0% utilized CTOR for image guidance at some point during their treatment. 21.2% utilized CTOR as the only image guidance technique, while 34.8% utilized CTOR in combination with kV planar imaging. For 43.9% of patients, only orthogonal planar kV imaging was utilized. Head and neck treatment sites most often utilized CTOR alone as an image guidance technique, while central nervous system sites most often utilized kV planar imaging alone. Of the patients who required new CT imaging for plan adaptation, 75.0% utilized CTOR images. Some reasons for patients not being able to utilize CTOR imaging for re-planning were the need for 4DCT imaging (which was not available on the CTOR) or the need to re-make immobilization devices (such as thermoplastic masks due to becoming loose). CTOR was shown to be utilized for image guidance in the majority of patients receiving proton therapy at a single-room proton therapy center. CTOR was able to be used for plan adaptation in a large majority of patients, eliminating the need to schedule additional CT simulation appointments for these patients.

A Novel Analytic Method of Automatically Assessing Beamline Geometric Range Variations for CBCT-Guided Intensity-Modulated Proton Therapy (IMPT) for Localized Prostate Cancer

A novel image-processing analytics software was introduced to quantitatively assess the beamline geometric range variations for proton spots around the planning target in daily CBCT-guided prostate IMPT. Three hundred eighty-seven consecutive full-CBCT alignment images of 11 localized prostate cancer IMPT cases were retrospectively analyzed to quantify the range variations of proton beamlines using a home-grown software. Each patient treatment comprises two proton scanning beams. All cases had a history of a plan revision with a re-simulated CT set. With this novel method the patient body surfaces are reconstructed by generating triangle mesh surfaces using a python Delaunay tessellation method. A python ray casting algorithm is utilized to determine the surface offset of the aligned CBCT relative to the planning CT. The proton beamlines are extrapolated from all the beam spots within 10 mm-enlarged planning target volume. The maximal geometric range variation was used to score the selected percentile of the included beamlines of the beam. The accuracy of this analytic software was satisfactorily validated prior to its application to this retrospective investigation. In practice, the proton range uncertainties are routinely estimated from their geometric range variations measured on a setup CBCT. The computation or processing time is about 60 seconds for each CBCT - planning CT analysis on a prostate IMPT positioning. The geometric range variations in the 95th percentile beamlines of 774 fractional beams or 387 aligned CBCT images are 3.29 ± 1.43 mm. As tabulated in table-1, worsened beam range variations of setup CBCTs were reduced by 2.60 ± 0.30 mm in the succeeding 2 fractions post using re-simulated setups. In this serial, an averaged 1.41 ± 0.10 mm range variation reduction was seen by re-simulation throughout the course. The geometric range variations of beamlines in prostate IMPT were comprehensively analyzed, for the first time, using a novel analytic software based on aligned daily CBCTs. The results of this study suggest that the re-simulated setups can be an effective way to reduce beamline range variations for localized prostate IMPT. Incorporation of this process for other IMPT treatment sites, as well as a Gamma-indexed analysis will be added in our immediate future research.

Multi-Institutional Phase I Feasibility Trial of Vertebral Body Sparing CSI for Pediatric Brain Tumors

Craniospinal irradiation (CSI) is an essential part of curative treatment for several pediatric brain tumors. Proton CSI allows for sparing of the organs anterior to the vertebral bodies (VBs), but this technique still includes the entire VB in the target for growing children. providing no advantage in marrow sparing or adverse effects on growth. Advances in proton therapy including Proton Beam Scanning (PBS) allow for delivery of proton CSI with substantial vertebral body sparing (VBS). We sought to determine the feasibility of VBS CSI using PBS based on the effects on tumor control and growth, and the occurrence of grade III/IV hematologic toxicity. Clinical and treatment characteristics were recorded for 20 pediatric patients with medulloblastoma (n = 14) or germ cell tumor (GCT) (n = 6) who received proton VBS CSI without concurrent chemotherapy or with concurrent single-agent vincristine in a multi-institutional clinical trial. The following standard variables were extracted for each patient: age, histology, radiation dose, chemotherapy regimen, and growth hormone replacement status. Complete blood counts (CBC) with differential and data on height/weight were recorded at baseline pre-RT, weekly during RT, and after completion of cancer treatment. Hematologic toxicity was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 4 (CTCAE v4). Median age of 13 male and 7 female patients receiving proton VBS CSI was 10 years (range: 5.1 - 15.1). All GCT patients (n = 6, 30%) received pre-RT chemo. Median CSI dose was 23.4 Gy (range: 21.0 - 37.8), and total dose to tumor bed was 54 Gy in 18 patients (90%) while 2 patients with pure germinoma received a total dose of 36 and 37.5 Gy, respectively. 11 patients (55%) did not receive concurrent vincristine. At a median follow up of 26.4 months (range: 12.5 - 56.3) from the start of RT, no patients relapsed. 17 patients (85%) developed grade ≥3 hematologic toxicity including grade 3 lymphopenia (n = 16), leukopenia (n = 9), neutropenia (n = 8), anemia (n = 1), and grade 4 neutropenia (n = 1). The patient who developed grade 4 neutropenia had low white blood counts prior to RT. 14 patients (70%) received post-RT chemo. No patients required platelet transfusion during RT. Those findings are similar to historical controls. 4 patients started growth hormone replacement therapy after RT. No patients developed spine deformities after the completion of treatment. Proton VBS CSI is a feasible and well tolerated treatment for children with brain tumors. Longer follow up is needed to assess for late effects on tumor control. It is too early to assess for height in this cohort but for the patients that had longer follow up, normal height was achieved.

Neurologic Events and Outcomes in Patients Receiving Proton and Photon Reirradiation for High Grade Non-Codeleted Gliomas

Patients undergoing reirradiation (ReRT) for high grade glioma are at risk for tumor progression, pseudoprogression, and radiation necrosis. We investigated factors associated with neurologic events and disease control after re-irradiation with protons and photons at a single academic center. We reviewed records and MRIs of patients receiving scanning beam proton (since center opening in 2016) and photon (since 2015) reirradiation in ≥10 fractions for grade 3 anaplastic astrocytoma (AA) and grade 4 glioblastoma (GBM), excluding 1p19q co-deleted oligodendrogliomas and extensive multifocal/leptomeningeal disease. The primary endpoint was time from ReRT to ≥ grade 2 pseudoprogression or radiation necrosis (PsP/RN, grade 2: moderate symptoms requiring outpatient steroids/bevacizumab, grade 3: severe symptoms leading to admission or surgical intervention). Dose was converted to EQD2 using a/b = 3. Cox proportional hazards model was used to calculate survival and time to PsP/RN. A total of 53 patients were included (26 protons, 27 photons, median KPS 80). Patients receiving protons had more favorable features. Compared to the photons, the proton group was younger (48 vs. 58) and more likely to have AA (46% vs. 22%) and resection within 3 months (42% vs 26%). The proton group also had a longer interval from prior RT (57 vs. 39 months) and were less likely to receive bevacizumab at reRT (15% vs. 59%). CTV was 130 cc for protons vs 99 cc for photons, and most had active disease at time of ReRT identified on planning MRI (76% protons, 85% photons). Median OS was 10.5 months (14.1 months protons, 8.1 months photons), with time from initial RT the only significant factor on multivariate analysis. Median PFS was 9.4 months (9.8 months protons, 6.2 months photons). 9 patients (18%) had ≥ grade 3 PsP/RN (8 proton, 1 photon) and 21 patients (41%) had ≥ grade 2 PsP/RN (16 proton, 5 photon). Grade 3 events included 1 seizure (photon group), 1 hemorrhage, 1 thalamic stroke, 1 shunt placement, 1 re-resection, and PSP4 4 PsP/RN requiring admission. Protons were associated shorter time to ≥ grade 2 PsP/RN (4 months vs. not reached, p = 0.027). When accounting for bevacizumab use at time of reRT, the association between protons and PsP/RN lost significance but there remained a trend (grade 2, p = 0.095, HR 2.4; grade 3, p = 0.105, HR 5.8). CTV, MGMT status, EQD2, and interval from prior RT were not associated with PsP/RN. High grade neurologic events were common in patients with predominantly active, unresected high grade gliomas receiving ReRT. Though ascertainment and survival bias are significant limitations, pseudoprogression and necrosis appeared to be more prominent in patients receiving protons. These results contribute to ongoing efforts to both optimize ReRT for high grade glioma and investigate biologic effects of proton therapy.

The Interplay Effect and Mitigations with Cyclotron and Linac Proton Beam Scanning for Lung SBRT

To evaluate the impact of different types of pencil beam scanning proton accelerators and spot sizes on interplay effects, mitigations, and plan quality for lung cancer patients treated with SBRT. Twenty lung cancer patients (ten peripheral and ten central tumors) treated in our institution with photon SBRT were selected to represent varying tumor volumes and respiratory motion amplitudes for this retrospective study. The respiratory motion amplitude ranged from 0.1 to 1.0 cm with compression. For each patient, plans were created using: 1) cyclotron-generated proton beams (CPB) (σ: 2.7-7.0 mm); 2) linear accelerator proton beams (LPB) (σ: 2.9-5.5 mm); and 3) linear accelerator proton minibeams (LPMB) (σ: 0.9-3.9 mm). Plans were robustly optimized on the GTV using each individual 4DCT phase. Single-filed optimization (SFO) plans were the first attempt, and if the plan quality did not meet the dosimetric requirement, multi-field optimization (MFO) was used. MFO plans were created for all patients for comparison. For each patient, all plans were normalized to have the same dose to 99% of the GTV. Interplay effects were evaluated for ten scenarios of treatment delivery starting in ten breathing phases using machine generic time models and a constant breathing period of 4 seconds. Volumetric repainting (VR) was performed 2-6 times for each plan. To assess plan quality in the nominal scenario, we compared the conformity index (CI), R50, and the percentage of lung volume receiving 20 Gy (RBE) (V20Gy). CI is defined as the ratio of the 100% isodose volume to the GTV. R50 is defined as the 50% isodose volume divided by the GTV. Dmax and V18Gy of the proximal bronchial tree (PBT) were evaluated for central tumors. Twelve of 20 plans can be optimized sufficiently with SFO. In interplay effect evaluation, the mean V100%RX values of the GTV were 99.42±0.6%, 97.52±3.9%, and 94.49±7.3%for CPB, LPB, and LPMB plans respectively. After VR 2/3/5 times, the V100%RX values were improved (on average) by 0.13%/1.84%/4.63% for CPB/LPB/LPMB plans. The delivery time for VR plans was the lowest for LPB plans, while delivery time for LPMB was on average 1 minute longer than CPB plans. VR showed no effect on lung V20Gy, Dmax and V18Gy of the PBT. SFO plans were more robust against the interplay effect compared with MFO plans for LPB and LPMB. Average CIs of 1.88±0.4, 1.79±0.4, and 1.75±0.4; average R50s of 7.99±4.0, 6.68±3.0, and 5.70±2.6; and average lung V20Gy values of 2.81±1.5, 2.26±1.3, and 1.85±1.1 were obtained for CPB, LPB, and LPMB plans, respectively. Dmax and V18Gy of the PBT decreased with decreasing spot sizes. LPMB, with the smallest spot size, produced superior plan quality. In the absence of VR, proton machines with large spot sizes generated more robust plans against interplay effects. VR improved the plan robustness against interplay effects for modalities with small spot sizes and fast energy changes, preserving the low dose sparing aspect of the LPMB, even when motion is included.

A portable primary-standard level graphite calorimeter for absolute dosimetry in clinical pencil beam scanning proton beams

Objective. To report the use of a portable primary standard level graphite calorimeter for direct dose determination in clinical pencil beam scanning proton beams, which forms part of the recommendations of the proposed Institute of Physics and Engineering in Medicine (IPEM) Code of Practice (CoP) for proton therapy dosimetry. Approach. The primary standard proton calorimeter (PSPC) was developed at the National Physical Laboratory (NPL) and measurements were performed at four clinical proton therapy facilities that use pencil beam scanning for beam delivery. Correction factors for the presence of impurities and vacuum gaps were calculated and applied, as well as dose conversion factors to obtain dose to water. Measurements were performed in the middle of 10 × 10 × 10 cm3 homogeneous dose volumes, centred at 10.0, 15.0 and 25.0 g·cm−2 depth in water. The absorbed dose to water determined with the calorimeter was compared to the dose obtained using PTW Roos-type ionisation chambers calibrated in terms of absorbed dose to water in 60Co applying the recommendations in the IAEA TRS-398 CoP. Main results. The relative dose difference between the two protocols varied between 0.4% and 2.1% depending on the facility. The reported overall uncertainty in the determination of absorbed dose to water using the calorimeter is 0.9% (k = 1), which corresponds to a significant reduction of uncertainty in comparison with the TRS-398 CoP (currently with an uncertainty equal or larger than 2.0% (k = 1) for proton beams). Significance. The establishment of a purpose-built primary standard and associated CoP will considerably reduce the uncertainty of the absorbed dose to water determination and ensure improved accuracy and consistency in the dose delivered to patients treated with proton therapy and bring proton reference dosimetry uncertainty in line with megavoltage photon radiotherapy.

Impact of Multiple Beams on the FLASH Effect in Soft Tissue and Skin in Mice

FLASH proton pencil beam scanning (p-PBS) showed a reduction in mouse skin toxicity and fibrosis when delivered as a single, uninterrupted, high-dose fraction. Clinical p-PBS treatment usually requires multiple beams to achieve good conformality, and these beams are separated by minutes to allow patient and equipment repositioning. We evaluate the impact of multibeam versus single-beam proton radiation on the FLASH sparing effect on skin toxicity. The right hind leg of 10-week-old female C57Bl/6j mice was irradiated using a Varian ProBeam proton beam scanning gantry system at conventional (1 Gy/s) or FLASH (100 Gy/s) average field dose rate. We scored the skin toxicity after different doses for 7 weeks. The treatment was delivered as 1, 2, or 3 equal beams with an interruption of 2 minutes. For each beam delivery, the equipment remained in the same position so that there was a full overlap of beams administered. Single-beam delivery confirmed a benefit for p-PBS FLASH in this model at 30, 35, and 40 Gy. At 30 and 35 Gy, a single beam interruption of 2 minutes (2×15 Gy or 2×17.5 Gy) reduced the FLASH sparing effect, which remained significant (P < .001). However, 2 interruptions (3×10 Gy or 3×11.6 Gy) abrogated the normal tissue sparing effect. Our results indicate that the FLASHsparing effect in areas of beam overlap can be compromised by interruptions in delivery time. Time gap between overlapping beams and spatial arrangement of the delivered beams are important parameters for FLASH studies. The effect of multibeam needs to be studied on different organs of interest.

Using immunotherapy to enhance the response of a C3H mammary carcinoma to proton radiation

Background The benefit of combining immunotherapy with photon irradiation has been shown pre-clinically and clinically. This current pre-clinical study was designed to investigate the anti-tumour action of combining immunotherapy with protons. Materials and Methods Male CDF1 mice, with a C3H mammary carcinoma inoculated on the right rear foot, were locally irradiated with single radiation doses when tumours reached 200mm3. Radiation was delivered with an 83–107MeV pencil scanning proton beam in the centre of a 3 cm spread out Bragg peak. Following irradiation (day 0), mice were injected intraperitoneal with anti-CTLA-4, anti-PD-1, or anti-PD-L1 (10 mg/kg) twice weekly for two weeks. Endpoints were tumour growth time (TGT3; time to reach 3 times treatment volume) or local tumour control (percent of mice showing tumour control at 90 days). A Student’s T-test (tumour growth) or Chi-squared test (tumour control) were used for statistical analysis; significance levels of p < 0.05. Results Untreated tumours had a mean (± 1 S.E.) TGT3 of 4.6 days (± 0.4). None of the checkpoint inhibitors changed this TGT3. A linear increase in TGT3 was seen with increasing radiation doses (5–20 Gy), reaching 17.2 days (± 0.7) with 20 Gy. Anti-CTLA-4 had no effect on radiation doses up to 15 Gy, but significantly enhanced 20 Gy; the TGT3 being 23.0 days (± 1.3). Higher radiation doses (35–60 Gy) were investigated using a tumour control assay. Logit analysis of the dose response curve, resulted in a TCD50 value (radiation dose causing 50% tumour control; with 95% confidence intervals) of 48 Gy (44–53) for radiation only. This significantly decreased to 43 Gy (38–49) when mice were treated with anti-CTLA-4. Neither anti-PD-1 nor anti-PD-L1 significantly affected tumour control. Conclusion Checkpoint inhibitors enhanced the response of this C3H mammary carcinoma to proton irradiation. However, this enhancement depended on the checkpoint inhibitor and radiation dose.

PO-1122 Simultaneous integrated boost with spot scanning proton beam irradiation for meningiomas

PO-1122 Simultaneous integrated boost with spot scanning proton beam irradiation for meningiomas

OC-0929 Scintillation imaging for time-resolved 2D monitoring of ultra-high dose rate proton beam scanning

OC-0929 Scintillation imaging for time-resolved 2D monitoring of ultra-high dose rate proton beam scanning

PO-1980 The interplay effect and mitigations with cyclotron and linac proton beam scanning for lung SBRT

PO-1980 The interplay effect and mitigations with cyclotron and linac proton beam scanning for lung SBRT

Design and characterization of an aperture system and spot configuration for ocular treatments with a gantry-based spot scanning proton beam.

Proton therapy is a key modality used in the treatment of ocular melanoma. Traditionally ocular sites are treated using a dedicated eyeline with a passively scattered proton beam and a brass aperture. This work aims to design and characterize a beam-collimating aperture to treat ocular targets with a gantry-based spot scanning proton beam. A plastic aperture system that slides into the gantry nozzle of a spot scanning proton beam was designed and constructed. It consists of an intermediate scraper layer to attenuate stray protons and a 3D-printed patient-specific aperture positioned 5.7cm from the surface of the eye. The aperture system was modeled in TOPAS and Monte Carlo simulations were validated with film measurements. Two different spot configurations were investigated for treatment planning and characterized based on lateral penumbra, central axis (CAX) dose and relative efficiency. Alignment and leakage were investigated through experimental film measurements. Range was verified using a multi-layer ionization chamber. Reference dose measurements were made with a PinPoint 3D ion chamber. Neutron dose was evaluated through Monte Carlo simulations. Aperture alignment with radiation isocenter was determined to be within 0.31mm at a gantry angle of 0°. A single-spot configuration with a 10mm diameter aperture yielded film-measured lateral penumbras of 1mm to 1.25mm, depending on depth in the spread-out Bragg peak. TOPAS simulations found that a single spot configuration results in a flat dose distribution for a 10mm diameter aperture and provides a CAX dose of less than 106% for apertures less than 14mm in diameter. For larger targets, adding four corner spots to fill in the dose distribution is beneficial. Trade-offs between lateral penumbra, CAX dose and relative efficiency were characterized for different spot configurations and can be used for future clinical decision-making. The aperture was experimentally determined to not affect proton beam range, and no concerning leakage radiation or neutron dose was identified. Reference dose measurements with a PinPoint ion chamber were within 2.1% of Monte Carlo calculated doses. The aperture system developed in this work provides a method of treating ocular sites on a gantry-based spot scanning proton system. Additional work to develop compatible gaze tracking and gating infrastructure is ongoing.

Study of a plastic scintillating plate-based quality assurance system for pencil beam scanning proton beams.

The purpose of this study was to evaluate a plastic scintillating plate-based beam monitoring system to perform quality assurance (QA) measurements in pencil beam scanning proton beam. Single spots and scanned fields were measured with the high-resolution dosimetry system, consisting of a plastic scintillation plate coupled to a camera in a dark box at the isocenter. The measurements were taken at 110-190 MeV beam energies with 30° gantry angle intervals at each energy. Spot positions were determined using the plastic scintillating plate-based dosimetry system at the isocenter for 70-230 MeV beam energies with 30° gantry angle intervals. The effect of gantry angle on dose distribution was also assessed by determining the scanning pattern for daily QA and 25 fields treated with intensity-modulated proton therapy. Spot size, field flatness, and field symmetry of plastic scintillating plate-based dosimetry system were consistent with EBT3 at all investigated energies and angles. In all investigated energies and angles, the spot size measured was ±10% of the average size of each energy, the spot position measured was within ±2 mm, field flatness was within ±2%, and field symmetry was within ±1%. The mean gamma passing rates with the 3%/3 mm gamma criterion of the scanning pattern and 25 fields were 99.2% and 99.8%, respectively. This system can be effective for QA determinations of spot size, spot position, field flatness, and field symmetry over 360° of gantry rotation in a time- and cost-effective manner, with spatial resolution comparable to that of EBT3 film.

A multi-source based Monte Carlo simulation model for spot scanning proton radiotherapy using GEANT4

Proton therapy is widely used for treating various tumor types due to its favorable dosimetric characteristics compared with conventional radiotherapy. However, a small error in dose calculation may lead to a substantial misadministration of planned radiation dose. This work aims to create a simplified and easy-to-use Monte Carlo (MC) simulation model, based on the multi-source model principle, for spot scanning proton radiotherapy. Our multi-source model contains a set of physical parameters acquired from a Varian ProBeam compact system at the South Florida Proton Therapy Institute (SFPTI). The source model input parameters are mean energy (σΕ) and beam spot (σs) standard deviations, which directly affect the integrated depth-dose (IDD) dosimetric characteristics such as beam width, proton range, and distal fall-off. Despite the simplicity of the presented model, all simulated results matched the corresponding experimental values within 2.5% and were found to be within the acceptable clinical limits, for a wide nominal proton energy range (i.e., 90–220 MeV). Additionally, the comparison of the simulated IDDs with the experimental IDDs was found to be highly conformal with 100% of the points passing the 2%/2 mm gamma index test. The model presented in this work can be efficiently used to model high energy (>80 MeV) in a central axis clinical scanning proton beam in a real clinical setting. The small number of input parameters selected allows for a more efficient and user-friendly MC modeling than previously developed models, while off-axis beam characteristics can be studied with the addition of a new sub-source parameter file.

Proton beam therapy in repeat irradiation of recurrent head and neck tumors: analysis of short-term results

Introduction. Recurrence of head and neck tumors occurs in 50 % of cases and usually has locoregional character. Due to the characteristics of dose distribution, proton beam therapy is a promising treatment option for patients with recurrences of tumors in this location who previously underwent radiation therapy.Aim. To evaluate the effectiveness and tolerability of repeat irradiation using active scanning proton beam therapy in patients with recurrent head and neck tumors who previously underwent radiation therapy.Materials and methods. Between November of 2015 and December of 2020, 40 patients with locoregional recurrence of head and neck tumors underwent treatment using active scanning proton beam therapy at the A. F . Tsyb Medical Radiological Research Center – branch of the National Medical Research Radiological Center. Median cumulative dose of primary irradiation was 64.5 Gy. Median time between primary and repeat irradiation was 35.7 months, mean irradiated volume of the repeat course was 94.5 cm3. Proton beam therapy was performed using standard mode (2 isoGy) and accelerated hypofractionation (2.4 isoGy / 3 isoGy) with mean equivalent cumulative dose of 56.4 Gy (α / β = 10). Radiation toxicity was evaluated using the Radiation Therapy Oncology Group European (RTOG) / Organization for Research and Treatment of Cancer (EORTC) scale.Results. Treatment response was achieved in 34 (85 %) patients: in 17 (42.5 %) patients, stable disease was observed; in 10 (25 %) patients, partial response was observed; and in 7 (17.5 %) patients, complete response was observed. In 6 (15 %) cases, disease progression was diagnosed at first follow-up examination. One- and two-year locoregional control, progression-free survival and overall survival were 58.4 / 19.8; 44.5 / 19.8 and 82.3 / 38.8 % respectively with median follow-up duration of 14.2 months. Median survival was 19.5 months. Grade III and above early radiation toxicity was observed in 3 (7.5 %) patients. In total, 6 (15 %) cases of grade III complications and 2 (5 %) episodes of carotid artery rupture leading to death were observed. Overall frequency of complications of grade III and higher was 20 %.Conclusion. Repeat irradiation using proton beam therapy can be considered an effective and safe treatment method for patients with recurrent head and neck tumors. Dosimetric and radiobiological benefits of proton beams allow to achieve balance between high doses and radiation exposure in previously irradiated tissues.

Erratum to: Optical Sensor for Measuring the Scanning Proton Beam Profile at the Prometheus Medical Accelerator

Erratum to: Optical Sensor for Measuring the Scanning Proton Beam Profile at the Prometheus Medical Accelerator

Ion recombination correction factors and detector comparison in a very-high dose rate proton scanning beam

PurposeAccurate dosimetry is paramount to study the FLASH biological effect since dose and dose rate are critical dosimetric parameters governing its underlying mechanisms. With the goal of assessing the suitability of standard clinical dosimeters in a very-high dose rate (VHDR) experimental setup, we evaluated the ion collection efficiency of several commercially available air-vented ionization chambers (IC) in conventional and VHDR proton irradiation conditions. MethodsA cyclotron at the Orsay Proton Therapy Center was used to deliver VHDR pencil beam scanning irradiation. Ion recombination correction factors (ks) were determined for several detectors (Advanced Markus, PPC05, Nano Razor, CC01) at the entrance of the plateau and at the Bragg peak, using the Niatel model, the Two-voltage method and Boag’s analytical formula for continuous beams. ResultsMean dose rates ranged from 4 Gy/s to 385 Gy/s, and instantaneous dose rates up to 1000 Gy/s were obtained with the experimental set-up. Recombination correction factors below 2 % were obtained for all chambers, except for the Nano Razor, at VHDRs with variations among detectors, while ks values were significantly smaller (0.8 %) for conventional dose rates. ConclusionsWhile the collection efficiency of the probed ICs in scanned VHDR proton therapy is comparable to those in the conventional regime with recombination coefficiens smaller than 1 % for mean dose rates up to 177 Gy/s, the reduction in collection efficiency for higher dose rates cannot be ignored when measuring the absorbed dose in pre-clinical proton scanned FLASH experiments and clinical trials.

Comparing Ultra-hypofractionated Proton versus Photon Therapy in Extremity Soft Tissue Sarcoma.

Recent single institution, phase II evidence has demonstrated the feasibility and efficacy of ultra-hypofractionated, preoperative photon therapy in 5 fractions for the treatment of soft tissue sarcoma (STS). Our purpose was to evaluate the dosimetric benefits of modern scanning beam proton therapy compared with conventional photon radiation therapy (RT) for the neoadjuvant treatment of adult extremity STS. Existing proton and photon plans for 11 adult patients with STS of the lower extremities previously treated preoperatively with neoadjuvant RT at our center were used to create proton therapy plans using Raystation Treatment Planning System v10.A. Volumes were delineated, and doses reported consistent with International Commission on Radiation Units and Measurements reports 50, 62, and 78. Target volumes were optimized such that 100% clinical target volume (CTV) was covered by 99% of the prescription dose. The prescribed dose was 30 Gy for PT and RT delivered in 5 fractions. For proton therapy, doses are reported in GyRBE = 1.1 Gy. The constraints for adjacent organs at risk (OARs) within 1 cm of the CTV were the following: femur V30Gy ≤ 50%, joint V30Gy < 50%, femoral head V30Gy ≤ 5 cm3, strip V12 ≤ 10%, and skin V12 < 50%. Target coverage goals, OAR constraints, and integral dose were compared by Student t test with P < .05 significance. A minimum 99% CTV coverage was achieved for all plans. OAR dose constraints were achieved for all proton and photon plans; however, mean doses to the femur (10.7 ± 8.5 vs 16.1 ± 7.7 GyRBE), femoral head (2.0 ± 4.4 vs 3.6 ± 6.4 GyRBE), and proximal joint (1.8 ± 2.4 vs 3.5 ± 4.4 GyRBE) were all significantly lower with PT vs intensity-modulated radiation therapy (IMRT) (all P < .05). Integral dose was significantly reduced for proton vs photon plans. Conformity and heterogeneity indices were significantly better for proton therapy. Proton therapy maintained target coverage while significantly reducing integral and mean doses to the proximal organs at risk compared with RT. Further prospective investigation is warranted to validate these findings and potential benefit in the management of adult STS.

High-Risk Non-Small Cell Lung Cancer Treated With Active Scanning Proton Beam Radiation Therapy and Immunotherapy

PurposeNon-small cell lung cancer (NSCLC) is a deadly malignancy that is frequently diagnosed in patients with significant medical comorbidities. When delivering local and regional therapy, an exceedingly narrow therapeutic window is encountered, which often precludes patients from receiving aggressive curative therapy. Radiation therapy advances including particle therapy have been employed in an effort to expand this therapeutic window. Here we report outcomes with the use of proton therapy with curative intent and immunotherapy to treat patients diagnosed with high-risk NSCLC. Methods and MaterialsPatients were determined to be high risk if they had severe underlying cardiopulmonary dysfunction, history of prior thoracic radiation therapy, and/or large volume or unfavorable location of disease (eg, bilateral hilar involvement, supraclavicular involvement). As such, patients were determined to be ineligible for conventional x-ray–based radiation therapy and were treated with pencil beam scanning proton beam therapy (PBS-PBT). Patients who demonstrated excess respiratory motion (ie, greater than 1 cm in any dimension noted on the 4-dimensional computed tomography simulation scan) were deemed to be ineligible for PBT. Toxicity was reported using the Common Terminology Criteria for Adverse Events (CTCAE), version 5.0. Overall survival and progression-free survival were calculated using the Kaplan-Meier method. ResultsA total of 29 patients with high-risk NSCLC diagnoses were treated with PBS-PBT. The majority (55%) of patients were defined as high risk due to severe cardiopulmonary dysfunction. Most commonly, patients were treated definitively to a total dose of 6000 cGy (relative biological effectiveness) in 30 fractions with concurrent chemotherapy. Overall, there were a total of 6 acute grade 3 toxicities observed in our cohort. Acute high-grade toxicities included esophagitis (n = 4, 14%), dyspnea (n = 1, 3.5%), and cough (n = 1, 3.5%). No patients developed grade 4 or higher toxicity. The majority of patients went on to receive immunotherapy, and high-grade pneumonitis was rare. Two-year progression-free and overall survival was estimated to be 51% and 67%, respectively. COVID-19 was confirmed or suspected to be responsible for 2 patient deaths during the follow-up period. ConclusionsRadical PBS-PBT treatment delivered in a cohort of patients with high-risk lung cancer with immunotherapy is feasible with careful multidisciplinary evaluation and rigorous follow-up.