Publications by authors named "Damien C Weber"

160 Publications

Combining rescanning and gating for a time-efficient treatment of mobile tumors using pencil beam scanning proton therapy.

Radiother Oncol 2021 Apr 8. Epub 2021 Apr 8.

Center for Proton Therapy, Paul Scherrer Institute (PSI), 5232 Villigen PSI, Switzerland. Electronic address:

Background And Purpose: Respiratory motion during proton therapy can severely degrade dose distributions, particularly due to interplay effects when using pencil beam scanning. Combined rescanning and gating treatments for moving tumors mitigates dose degradation, but at the cost of increased treatment delivery time. The objective of this study was to identify the time efficiency of these dose degradation-motion mitigation strategies for different range of motions.

Materials And Methods: Seventeen patients with thoracic or abdominal tumors were studied. Tumor motion amplitudes ranged from 2-30 mm. Deliveries using different combinations of rescanning and gating were simulated with a dense dose spot grid (4x4x2.5 mm) for all patients and a sparse dose spot grid (8x8x5 mm) for six patients with larger tumor movements (>8 mm). The resulting plans were evaluated in terms of CTV coverage and time efficiency.

Results: Based on the studied patient cohort, it has been shown that for amplitudes up to 5 mm, no motion mitigation is required with a dense spot grid. For amplitudes between 5 and 10 mm, volumetric rescanning should be applied while maintaining a 100% duty cycle when using a dense spot grid. Although gating could be envisaged to reduce the target volume for intermediate motion, it has been shown that the dose to normal tissues would only be reduced marginally. Moreover, the treatment time would increase. Finally, for larger motion amplitudes, both volumetric rescanning and respiratory gating should be applied with both spot grids. In addition, it has been shown that a dense spot grid delivers better CTV dose coverage than a sparse dose grid.

Conclusion: Volumetric rescanning and/or respiratory gating can be used in order to effectively and efficiently mitigate dose degradation due to tumor movement.
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http://dx.doi.org/10.1016/j.radonc.2021.03.041DOI Listing
April 2021

Effects of deep inspiration breath hold on prone photon or proton irradiation of breast and regional lymph nodes.

Sci Rep 2021 Mar 16;11(1):6085. Epub 2021 Mar 16.

Department of Human Structure and Repair, Faculty of Medicine and Health Sciences, Ghent University, Radiotherapiepark, Corneel Heymanslaan 10, 9000, Ghent, Belgium.

We report on a comparative dosimetrical study between deep inspiration breath hold (DIBH) and shallow breathing (SB) in prone crawl position for photon and proton radiotherapy of whole breast (WB) and locoregional lymph node regions, including the internal mammary chain (LN_MI). We investigate the dosimetrical effects of DIBH in prone crawl position on organs-at-risk for both photon and proton plans. For each modality, we further estimate the effects of lung and heart doses on the mortality risks of different risk profiles of patients. Thirty-one patients with invasive carcinoma of the left breast and pathologically confirmed positive lymph node status were included in this study. DIBH significantly decreased dose to heart for photon and proton radiotherapy. DIBH also decreased lung doses for photons, while increased lung doses were observed using protons because the retracting heart is displaced by low-density lung tissue. For other organs-at-risk, DIBH resulted in significant dose reductions using photons while minor differences in dose deposition between DIBH and SB were observed using protons. In patients with high risks for cardiac and lung cancer mortality, average thirty-year mortality rates from radiotherapy-related cardiac injury and lung cancer were estimated at 3.12% (photon DIBH), 4.03% (photon SB), 1.80% (proton DIBH) and 1.66% (proton SB). The radiation-related mortality risk could not outweigh the ~ 8% disease-specific survival benefit of WB + LN_MI radiotherapy in any of the assessed treatments.
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http://dx.doi.org/10.1038/s41598-021-85401-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7966795PMC
March 2021

Proton Therapy for Intracranial Meningioma for the Treatment of Primary/Recurrent Disease Including Re-Irradiation.

Front Oncol 2020 14;10:558845. Epub 2020 Dec 14.

Department of Neurosurgery, The Walton Centre NHS Foundation Trust, Liverpool, United Kingdom.

Meningeal tumors represent approximately 10-25% of primary brain tumors and occur usually in elderly female patients. Most meningiomas are benign (80-85%) and for symptomatic and/or large tumors, surgery, with or without radiation therapy (RT), has been long established as an effective means of local tumor control. RT can be delivered to inoperable lesions or to those with non-benign histology and for Simpson I-III and IV-V resection. RT can be delivered with photons or particles (protons or carbon ions) in stereotactic or non-stereotactic conditions. Particle therapy delivered for these tumors uses the physical properties of charged carbon ions or protons to spare normal brain tissue (i.e. Bragg peak), with or without or a dose-escalation paradigm for non-benign lesions. PT can substantially decrease the dose delivered to the non-target brain tissues, including but not limited to the hippocampi, optic apparatus or cochlea. Only a limited number of meningioma patients have been treated with PT in the adjuvant or recurrent setting, as well as for inoperable lesions with pencil beam scanning and with protons only. Approximately 500 patients with image-defined or WHO grade I meningioma have been treated with protons. The reported outcome, usually 5-year local tumor control, ranges from 85 to 99% (median, 96%). For WHO grade II or III patients, the outcome of only 97 patients has been published, reporting a median tumor local control rate of 52% (range, 38-71.1). Only 24 recurring patients treated previously with photon radiotherapy and re-treated with PT were reported. The clinical outcome of these challenging patients seems interesting, provided that they presented initially with benign tumors, are not in the elderly category and have been treated previously with conventional radiation dose of photons. Overall, the number of meningioma patients treated or-re-irradiated with this treatment modality is small and the clinical evidence level is somewhat low (i.e. 3b-5). In this review, we detail the results of upfront PT delivered to patients with meningioma in the adjuvant setting and for inoperable tumors. The outcome of meningioma patients treated with this radiation modality for recurrent tumors, with or without previous RT, will also be reviewed.
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http://dx.doi.org/10.3389/fonc.2020.558845DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7769250PMC
December 2020

Liver-ultrasound-guided lung tumour tracking for scanned proton therapy: a feasibility study.

Phys Med Biol 2021 Jan 26;66(3):035011. Epub 2021 Jan 26.

Center for Proton Therapy, Paul Scherrer Institute (PSI), Villigen PSI, Switzerland. Department of Physics, ETH Zurich, Zurich, Switzerland.

Pencil beam scanned (PBS) proton therapy of lung tumours is hampered by respiratory motion and the motion-induced density changes along the beam path. In this simulation study, we aim to investigate the effectiveness of proton beam tracking for lung tumours both under ideal conditions and in conjunction with a respiratory motion model guided by real-time ultrasound imaging of the liver. Multiple-breathing-cycle 4DMRIs of the thorax and abdominal 2D ultrasound images were acquired simultaneously for five volunteers. Deformation vector fields extracted from the 4DMRI, referred to as ground truth motion, were used to generate 4DCT(MRI) data sets of two lung cancer patients, resulting in 10 data sets with variable motion patterns. Given the 4DCT(MRI) and the corresponding ultrasound images as surrogate data, a patient-specific motion model was built. The model consists of an autoregressive model and Gaussian process regression for the temporal and spatial prediction, respectively. Two-field PBS plans were optimised on the reference CTs, and 4D dose calculations (4DDC) were used to simulate dose delivery for (a) unmitigated motion, (b) ideal 2D and 3D tracking (both beam adaption and 4DDC based on ground truth motion), and (c) realistic 2D and 3D tracking (beam adaption based on motion predictions, 4DDC on ground truth motion). Model-guided tracking retrieved clinically acceptable target dose homogeneity, as seen in a substantial reduction of the D5%-D95% compared to the non-mitigated simulation. Tracking in 2D and 3D resulted in a similar improvement of the dose homogeneity, as did ideal and realistic tracking simulations. In some cases, however, the tracked deliveries resulted in a shift towards higher or lower dose levels, leading to unacceptable target over- or under-coverage. The presented motion modelling framework was shown to be an accurate motion prediction tool for the use in proton beam tracking. Tracking alone, however, may not always effectively mitigate motion effects, making it necessary to combine it with other techniques such as rescanning.
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http://dx.doi.org/10.1088/1361-6560/abcde6DOI Listing
January 2021

Dosimetric analysis of local failures in skull-base chordoma and chondrosarcoma following pencil beam scanning proton therapy.

Radiat Oncol 2020 Nov 16;15(1):266. Epub 2020 Nov 16.

Center for Proton Therapy, Paul Scherrer Institute, ETH Domain, Forschungsstrasse 111, 5232, Villigen, Switzerland.

Background: Despite combined modality treatment involving surgery and radiotherapy, a relevant proportion of skull-base chordoma and chondrosarcoma patients develop a local recurrence (LR). This study aims to analyze patterns of recurrence and correlate LR with a detailed dosimetric analysis.

Methods: 222 patients were treated with proton radiotherapy for chordoma (n = 151) and chondrosarcoma (n = 71) at the PSI between 1998 and 2012. All patients underwent surgery, followed by pencil-beam scanning proton therapy to a mean dose of 72.5 ± 2.2Gy. A retrospective patterns of recurrence analysis was performed: LR were contoured on follow-up MRI, registered with planning-imaging and the overlap with initial target structures (GTV, PTV, PTV) was calculated. DVH parameters of planning structures and recurrences were calculated and correlated with LR using univariate and multivariate cox regression.

Results: After a median follow-up of 50 months, 35 (16%) LR were observed. Follow-up MRI imaging was available for 27 (77%) of these recurring patients. Only one (3.7%) recurrence was located completely outside the initial PTV (surgical pathway recurrence). The mean proportions of LR covered by the initial target structures were 48% (range 0-86%) for the GTV, 70% (range 0-100%) for PTV and 83% (range 0-100%) for PTV. In the univariate analysis, the following DVH parameters were significantly associated with LR: GTV(V < 66Gy, p = 0.01), GTV(volume, p = 0.02), PTV(max, p = 0.02), PTV(V < 66Gy, p = 0.03), PTV(V < 59Gy, p = 0.02), PTV(volume, p = 0.01) and GTV(D95, p = 0.05). In the multivariate analysis, only histology (chordoma vs. chondrosarcoma, p = 0.01), PTV(volume, p = 0.05) and GTV(V < 66Gy, p = 0.02) were independent prognostic factors for LR.

Conclusion: This study identified DVH parameters, which are associated with the risk of local recurrence after proton therapy using pencil-beam scanning for patients with skull-base chordoma and chondrosarcoma.
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http://dx.doi.org/10.1186/s13014-020-01711-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7670611PMC
November 2020

Good long-term visual outcomes of parapapillary choroidal melanoma patients treated with proton therapy: a comparative study.

Int Ophthalmol 2021 Feb 25;41(2):441-452. Epub 2020 Sep 25.

Department of Ophthalmology, University of Lausanne, Jules-Gonin Eye Hospital, Fondation Asile des Aveugles, Lausanne, Switzerland.

Purpose: To evaluate why small- and certain medium-sized parapapillary choroidal melanoma (pcM) patients treated with hypo-fractionated proton therapy (PT) retain excellent long-term visual acuity (VA) and assess the negative predictive factors for retaining good vision (≤ 0.2 logMAR (≥ 0.6 decimal) after 5 years.

Methods: This single-center, retrospective, comparative study recruited consecutive pcM patients that were treated with PT. Between 1984 and 2005, 609 patients received a total of 60 CGE, of whom 310 met the following inclusion criteria: posterior tumor border ≤ 2.5 mm from the optic disc, largest tumor diameter ≤ 17.9 mm, tumor thickness ≤ 5.2 mm and available follow-up data for at least 5 years.

Results: Mean follow-up was 120.8 ± 48.8 months (54.0-295.0). Out of 310 patients, 64 (21%) maintained a VA ≤ 0.2 logMAR (≥ 0.6 decimal) for at least 5 years following PT and were allocated to the "good visual outcome" (GVO) group, while the remaining 246 (79%) constituted the "poor visual outcome" (PVO) group, subdivided into 70 (22%) with a VA of 0.3-1.0 logMAR (0.1-0.5 decimal) and 157 (57%) patients with a VA > 1.0 logMAR (< 0.1 decimal). On multivariate analysis, older age (P = 0.04), tumor localization ≤ 0.5 mm to the fovea (P < 0.03), volume of the optic disc and macula receiving 50% of dose (30 CGE) (P = 0.02 and P < 0.001, respectively) were independent negative predictors of GVO.

Conclusions: Of 310 small- to medium-sized pcM patients successfully treated with PT, 21% retained a VA ≤ 0.2 logMAR (≥ 0.6 decimal) for at least 5 years. Strongest negative predictive factor for retaining good long-term vision was the volume of the macula irradiated with at least 30 Gy.
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http://dx.doi.org/10.1007/s10792-020-01594-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7882567PMC
February 2021

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

Pediatr Blood Cancer 2020 12 2;67(12):e28664. Epub 2020 Sep 2.

Center for Proton Therapy, Paul Scherrer Institute, Villigen, Switzerland.

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.
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http://dx.doi.org/10.1002/pbc.28664DOI Listing
December 2020

Commissioning and Quality Assurance of a novel solution for respiratory-gated PBS proton therapy based on optical tracking of surface markers.

Z Med Phys 2020 Aug 20. Epub 2020 Aug 20.

Center for Proton Therapy, Paul Scherrer Institute, 5232 Villigen, Switzerland.

We present the commissioning and quality assurance of our clinical protocol for respiratory gating in pencil beam scanning proton therapy for cancer patients with moving targets. In a novel approach, optical tracking has been integrated in the therapy workflow and used to monitor respiratory motion from multiple surrogates, applied on the patients' chest. The gating system was tested under a variety of experimental conditions, specific to proton therapy, to evaluate reaction time and reproducibility of dose delivery control. The system proved to be precise in the application of beam gating and allowed the mitigation of dose distortions even for large (1.4cm) motion amplitudes, provided that adequate treatment windows were selected. The total delivered dose was not affected by the use of gating, with measured integral error within 0.15cGy. Analysing high-resolution images of proton transmission, we observed negligible discrepancies in the geometric location of the dose as a function of the treatment window, with gamma pass rate greater than 95% (2%/2mm) compared to stationary conditions. Similarly, pass rate for the latter metric at the 3%/3mm level was observed above 97% for clinical treatment fields, limiting residual movement to 3mm at end-exhale. These results were confirmed in realistic clinical conditions using an anthropomorphic breathing phantom, reporting a similarly high 3%/3mm pass rate, above 98% and 94%, for regular and irregular breathing, respectively. Finally, early results from periodic QA tests of the optical tracker have shown a reliable system, with small variance observed in static and dynamic measurements.
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http://dx.doi.org/10.1016/j.zemedi.2020.07.001DOI Listing
August 2020

Liver-ultrasound based motion modelling to estimate 4D dose distributions for lung tumours in scanned proton therapy.

Phys Med Biol 2020 12 22;65(23):235050. Epub 2020 Dec 22.

Department of Biomedical Engineering, University of Basel, Allschwil, Switzerland. Center for Medical Image Analysis & Navigation, University of Basel, Allschwil, Switzerland. Both authors contributed equally.

Motion mitigation strategies are crucial for scanned particle therapy of mobile tumours in order to prevent geometrical target miss and interplay effects. We developed a patient-specific respiratory motion model based on simultaneously acquired time-resolved volumetric MRI and 2D abdominal ultrasound images. We present its effects on 4D pencil beam scanned treatment planning and simulated dose distributions. Given an ultrasound image of the liver and the diaphragm, principal component analysis and Gaussian process regression were applied to infer dense motion information of the lungs. 4D dose calculations for scanned proton therapy were performed using the estimated and the corresponding ground truth respiratory motion; the differences were compared by dose difference volume metrics. We performed this simulation study on 10 combined CT and 4DMRI data sets where the motion characteristics were extracted from 5 healthy volunteers and fused with the anatomical CT data of two lung cancer patients. Median geometrical estimation errors below 2 mm for all data sets and maximum dose differences of [Formula: see text] = 43.2% and [Formula: see text] = 16.3% were found. Moreover, it was shown that abdominal ultrasound imaging allows to monitor organ drift. This study demonstrated the feasibility of the proposed ultrasound-based motion modelling approach for its application in scanned proton therapy of lung tumours.
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http://dx.doi.org/10.1088/1361-6560/abaa26DOI Listing
December 2020

Clinical outcomes of head and neck adenoid cystic carcinoma patients treated with pencil beam-scanning proton therapy.

Oral Oncol 2020 08 12;107:104752. Epub 2020 May 12.

Center for Proton Therapy, Paul Scherrer Institute, Villigen PSI, Switzerland; Radiation Oncology Department, University Hospital Zürich, Zürich, Switzerland; Radiation Oncology Department, University Hospital Bern, Inselspital, Bern, Switzerland. Electronic address:

Objective: The aim of this study was to evaluate the outcome of patients with head and neck adenoid cystic carcinoma (ACC) treated using pencil beam scanning proton therapy (PBS PT) at our institution.

Materials And Methods: Thirty-five patients who underwent treatment with PBS PT for ACC between 2001 and 2017 were included. Local control (LC), distant control (DC), progression-free survival (PFS), overall survival (OS) and their prognostic factors were evaluated. Adverse effects were prospectively assessed.

Results: The median patient follow-up was 30 months. Prior to PT, 26 patients (74.3%) underwent surgery with R0/R1/R2 outcome in 5, 13 and 8 cases, respectively. Nine patients (25.7%) presented with inoperable disease. The 2-year LC, DC, PFS and OS was 92.2%, 77.8%, 74.3% and 88.8%, respectively. LC was influenced by patient age (p = 0.002) with a significant difference between local and distant failure (median 61.3 vs. 42.3 years, p = 0.005). Tumor T stage was a significant risk factor for PFS (p = 0.045) and tumor prognostic group affected OS (p = 0.049). No significant survival advantage for operable vs. inoperable disease could be identified. The acute and late grade 3 toxicity rates were 14.3% and 6.1%, respectively. No acute or late grade 4/5 toxicities were observed.

Conclusions: PBS PT is an effective and safe treatment for patients with head & neck ACC in both definitive and adjuvant setting. Distant metastases are the main pattern of failure. Age, tumor stage and clinical stage had a significant negative impact on LC, OS and PFS.
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http://dx.doi.org/10.1016/j.oraloncology.2020.104752DOI Listing
August 2020

Pencil beam scanning proton therapy for the treatment of craniopharyngioma complicated with radiation-induced cerebral vasculopathies: A dosimetric and linear energy transfer (LET) evaluation.

Radiother Oncol 2020 08 5;149:197-204. Epub 2020 May 5.

Center for Proton Therapy, Paul Scherrer Institute, ETH Domain, Villigen, Switzerland; Department of Radiation Oncology, University Hospital of Zürich, Zürich, Switzerland; Department of Radiation Oncology, University Hospital of Bern, Bern, Switzerland.

Background And Purpose: This study analyses the dosimetric and dose averaged Linear Energy transfer (LETd) correlation in paediatric craniopharyngioma (CP) patients with and without radiation-induced cerebral vasculopathies (RICVs) treated with pencil beam scanning (PBS) proton therapy (PT).

Material And Methods: We reviewed a series of 16 CP patients treated with PT to a median dose of 54 Gy(RBE). Two (12.5%) index patients presented RICVs 14 and 24 months (median, 19) after PT. Organs at risks (OARs) as bilateral internal carotid arteries (ICAs) and circle of Willis were contoured based on CTs and MRIs pre- and post-PT. Dosimetry was reviewed and LETd distributions were calculated; LETd metric for PTVs and OARs were analysed. For a sub-cohort, dosimetric and LETd values robustness due to range uncertainties were computed.

Results: For the two index patients, no correlation was observed between RICVs and OARs doses. However for those patients mean(maximum) LETd values in the affected OARs were up to 4.0 ± 0.4 (7.8 ± 0.1)keV/μm; those LETd values were significantly higher (p = 0.02) than the mean(maximum) LETd values for the rest of the cohort (mean: 3.1 ± 0.3, maximum: 4.8 ± 1.0 keV/μm). This was due to asymmetric field arrangement, thus resulting in marked asymmetric LETd distributions. For such arrangement, maximum LETd values variations in vascular structures due to range uncertainties were up to 1.2 keV/μm, whilst for the symmetric one they were up to 0.7 keV/μm.

Conclusions: For children with and without RICVs, quantitative analysis showed a significant correlation with LETd average/maximum values in vascular structures, whilst no correlation was found on dosimetric parameters.
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http://dx.doi.org/10.1016/j.radonc.2020.04.052DOI Listing
August 2020

Prognostic impact of the "Sekhar grading system for cranial Chordomas" in patients treated with pencil beam scanning proton therapy: an institutional analysis.

Radiat Oncol 2020 May 6;15(1):96. Epub 2020 May 6.

Center for Proton Therapy, Paul Scherrer Institute, 5232 PSI West, Villigen, Switzerland.

Background: Skull base chordomas are rare and heterogeneously behaving tumors. Though still classified as benign they can grow rapidly, are locally aggressive, and have the potential to metastasize. To adapt the treatment to the specific needs of patients at higher risk of recurrence, a pre-proton therapy prognostic grading system would be useful. The aim of this retrospective analysis is to assess prognostic factors and the "Sekhar Grading System for Cranial Chordomas" (SGSCC) by evaluating the larger cohort of patients treated at our institution as to determine its reproducibility and ultimately to ensure more risk adapted local treatments for these challenging tumors.

Methods: We analyzed 142 patients treated for skull base chordomas between 2004 and 2016. We focused the analysis on the 5 criteria proposed for the SGSCC (tumor size, number of anatomic regions and vessels involved, intradural invasion, as well as recurrence after prior treatment) and classified our patients according to their score (based on the above mentioned criteria) into three prognostic groups, low-risk, intermediate-risk and high-risk. The three groups were then analyzed in regards of local control, local recurrence-free survival and overall survival.

Results: The median follow up was 52 months (range, 3-152). We observed 34 (24%) patients with a local recurrence, resulting in a local control of 75% at 5 years. Overall survival was 83% at 5 years, 12 (9%) patients had died due to local progression. When split into the three prognostic groups according to the SGSCC the observed local control was 90, 72 and 64% (p = 0.07) in the low-, intermediate- and high-risk group, respectively. A similar correlation was observed for local recurrence-free survival with 93, 89 and 66% (p = 0.05) and for overall survival with 89, 83 and 76% (p = 0.65) for the same prognostic groups.

Conclusions: After splitting our patient cohort into the three SGSCC risk groups, we found a trend towards better outcome for those patients with lower as opposed to higher scores. These results suggest that this prognostic grading system published by Sekhar et al. could be integrated in the management decision-tree for patients with skull base chordoma.
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http://dx.doi.org/10.1186/s13014-020-01547-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7201750PMC
May 2020

Practice Considerations for Proton Beam Radiation Therapy of Uveal Melanoma During the Coronavirus Disease Pandemic: Particle Therapy Co-Operative Group Ocular Experience.

Adv Radiat Oncol 2020 Jul-Aug;5(4):682-686. Epub 2020 Apr 23.

Nuffield Laboratory of Ophthalmology, Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, United Kingdom.

Uveal melanoma (UM) is a rare but life-threatening cancer of the eye. In light of the coronavirus disease (COVID-19) pandemic, hospitals and proton eye therapy facilities must analyze several factors to ensure appropriate treatment protocols for patients and provider teams. Practice considerations to limit COVID-19 transmission in the proton ocular treatment setting for UM are necessary. The Particle Therapy Co-Operative Group is the largest international community of particle/proton therapy providers. Participating experts have current or former affiliation with the member institutions of the Particle Therapy Co-Operative Group Ocular subcommittee with long-standing high-volume proton ocular programs. The practices reviewed in this document must be taken in conjunction with local hospital procedures, multidisciplinary recommendations, and regional/national guidelines, as each community may have its unique needs, supplies, and protocols. Importantly, as the pandemic evolves, so will the strategies and recommendations. Given the unique circumstances for UM patients, along with indications of potential ophthalmologic transmission as a result of health care providers working in close proximity to patients and intrinsic infectious risk from eyelashes, tears, and hair, practice strategies may be adapted to reduce the risk of viral transmission. Certainly, providers and health care systems will continue to examine and provide as safe and effective care as possible for patients in the current environment.
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http://dx.doi.org/10.1016/j.adro.2020.04.010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7179507PMC
April 2020

The European Organisation for Research and Treatment of Cancer, State of Science in radiation oncology and priorities for clinical trials meeting report.

Eur J Cancer 2020 05 16;131:76-88. Epub 2020 Apr 16.

Paul Scherrer Institute, ETH Domain, Villigen, Switzerland.

Background: New technologies and techniques in radiation oncology and imaging offer opportunities to enhance the benefit of loco-regional treatments, expand treatment to new patient populations such as those with oligometastatic disease and decrease normal tissue toxicity. Furthermore, novel agents have become available which may be combined with radiation therapy, and identification of radiation-related biomarkers can be studied to refine treatment prescriptions. Finally, the use of artificial intelligence (AI) capabilities may also improve treatment quality assurance or the ease with which radiation dosing is prescribed. All of these potential advances present both opportunities and challenges for academic clinical researchers.

Methods: Recently, the European Organisation for Research and Treatment of Cancer addressed these topics in a meeting of multiple stakeholders from Europe and North America. The following five themes radiobiology-based biomarkers, new technologies - particularly proton beam therapy, combination systemic and radiation therapy, management of oligometastatic disease and AI opportunities in radiation oncology were discussed in a State of Science format to define key controversies, unanswered questions and propose clinical trial priorities for development.

Conclusions: Priorities for clinical trials implementing new science and technologies have been defined. Solutions to integrate the multidimensional complexity of data have been explored. New types of platforms and partnerships can support innovative approaches for clinical research in radiation oncology.
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http://dx.doi.org/10.1016/j.ejca.2020.02.050DOI Listing
May 2020

Particle therapy in Europe.

Mol Oncol 2020 07 22;14(7):1492-1499. Epub 2020 Apr 22.

Paul Scherrer Institute, Villigen, Switzerland.

Particle therapy using protons or heavier ions is currently the most advanced form of radiotherapy and offers new opportunities for improving cancer care and research. Ions deposit the dose with a sharp maximum - the Bragg peak - and normal tissue receives a much lower dose than what is delivered by X-ray therapy. Particle therapy has also biological advantages due to the high linear energy transfer of the charged particles around the Bragg peak. The introduction of particle therapy has been slow in Europe, but within the last decade, more than 20 clinical facilities have opened and facilitated access to this frontline therapy. In this review article, the basic concepts of particle therapy are reviewed along with a presentation of the current clinical indications, the European clinical research, and the established networks.
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http://dx.doi.org/10.1002/1878-0261.12677DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7332216PMC
July 2020

Shortening delivery times for intensity-modulated proton therapy by reducing the number of proton spots: an experimental verification.

Phys Med Biol 2020 05 11;65(9):095008. Epub 2020 May 11.

Center for Proton Therapy, Paul Scherrer Institute, Villigen PSI, Switzerland.

Delivery times of intensity-modulated proton therapy (IMPT) can be shortened by reducing the number of spots in the treatment plan, but this may affect clinical plan delivery. Here, we assess the experimental deliverability, accuracy and time reduction of spot-reduced treatment planning for a clinical case, as well as its robustness. For a single head-and-neck cancer patient, a spot-reduced plan was generated and compared with the conventional clinical plan. The number of proton spots was reduced using the iterative 'pencil beam resampling' technique. This involves repeated inverse optimization, while adding in each iteration a small sample of randomly selected spots and subsequently excluding low-weighted spots until plan quality deteriorates. Field setup was identical for both plans and comparable dosimetric quality was a prerequisite. Both IMPT plans were delivered on PSI Gantry 2 and measured in water, while delivery log-files were used to extract delivery times and reconstruct the delivered dose via Monte-Carlo dose calculations. In addition, robustness simulations were performed to assess sensitivity to machine inaccuracies and errors in patient setup and proton range. The number of spots was reduced by 96% (from 33 855 to 1510 in total) without compromising plan quality. The spot-reduced plan was deliverable on our gantry in standard clinical mode and resulted in average delivery times per field being shortened by 46% (from 51.2 to 27.6 s). For both plans, differences between measured and calculated dose were within clinical tolerance for patient-specific verifications and Monte-Carlo dose reconstructions were in accordance with clinical experience. The spot-reduced plan was slightly more sensitive to machine inaccuracies, but more robust against setup and range errors. In conclusion, for an example head-and-neck case, spot-reduced IMPT planning provided a deliverable treatment plan and enabled considerable shortening of the delivery time (∼50%) without compromising plan quality or delivery accuracy, and without substantially affecting robustness.
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http://dx.doi.org/10.1088/1361-6560/ab7e7cDOI Listing
May 2020

Role of Complex Networks for Integrating Medical Images and Radiomic Features of Intracranial Ependymoma Patients in Response to Proton Radiotherapy.

Front Med (Lausanne) 2019 17;6:333. Epub 2020 Jan 17.

Center for Computational Science, University of Miami, Coral Gables, FL, United States.

Human cancers exhibit phenotypic diversity that medical imaging can precisely and non-invasively detect. Multiple factors underlying innovations and progresses in the medical imaging field exert diagnostic and therapeutic impacts. The emerging field of radiomics has shown unprecedented ability to use imaging information in guiding clinical decisions. To achieve clinical assessment that exploits radiomic knowledge sources, integration between diverse data types is required. A current gap is the accuracy with which radiomics aligns with clinical endpoints. We propose a novel methodological approach that synergizes data volumes (images), tissue-contextualized information breadth, and network-driven resolution depth. Following the Precision Medicine paradigm, disease monitoring and prognostic assessment are tackled at the individual level by examining medical images acquired from two patients affected by intracranial ependymoma (with and without relapse). The challenge of spatially characterizing intratumor heterogeneity is tackled by a network approach that presents two main advantages: (a) Increased detection in the image domain power from high spatial resolution, (b) Superior accuracy in generating hypotheses underlying clinical decisions.
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http://dx.doi.org/10.3389/fmed.2019.00333DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6978687PMC
January 2020

Impact of internal target volume definition for pencil beam scanned proton treatment planning in the presence of respiratory motion variability for lung cancer: A proof of concept.

Radiother Oncol 2020 04 30;145:154-161. Epub 2020 Jan 30.

Center for Proton Therapy, Paul Scherrer Institute (PSI), Villigen PSI, Switzerland.

Purpose: Motion management is crucial in scanned proton therapy for mobile tumours. Current motion mitigation approaches rely on single 4DCTs before treatment, ignoring respiratory variability. We investigate the consequences of respiratory variations on internal target volumes (ITV) definition and motion mitigation efficacy, and propose a probabilistic ITV based on 4DMRI.

Materials And Methods: Four 4DCT(MRI) datasets, each containing 40 variable cycles of synthetic 4DCTs, were generated by warping single-phase CTs of two lung patients with motion fields extracted from two 4DMRI datasets. Two-field proton treatment plans were optimised on ITVs based on different parts of the 4DCT(MRI)s. 4D dose distributions were calculated by considering variable respiratory patterns. Different probabilistic ITVs were created by incorporating the voxels covered by the CTV in at least 25%, 50%, or 75% (ITV25, ITV50, ITV75) of the cycles, and compared with the conservative ITV encompassing all possible CTV positions.

Results: Depending on the selected planning 4DCT, ITV volumes vary up to 20%, resulting in significant variation in CTV coverage for 4D treatments. Target coverage and homogeneity improved with the conservative ITV, but was associated with significantly increased lung dose (~1%). ITV25 and ITV50 led to acceptable plan quality in most cases without lung dose increments. ITV75 best minimised lung dose, but was insufficient to ensure coverage under all motion scenarios.

Conclusion: Irregular respiration significantly affects CTV coverage when ITVs are only defined by single 4DCTs. A probabilistic ITV50 provides an adequate compromise between target coverage and lung dose for most motion and patient scenarios investigated.
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http://dx.doi.org/10.1016/j.radonc.2019.12.001DOI Listing
April 2020

Prognostic factors for spinal chordomas and chondrosarcomas treated with postoperative pencil-beam scanning proton therapy: a large, single-institution experience.

J Neurosurg Spine 2020 Jan 31:1-10. Epub 2020 Jan 31.

1Center for Proton Therapy, Paul Scherrer Institute, Villigen.

Objective: The aim of this paper was to evaluate the prognostic factors in surgical and adjuvant care for spinal chordomas and chondrosarcomas after surgery followed by high-dose pencil-beam scanning proton therapy (PBS-PT).

Methods: From 1997 to 2016, 155 patients (61 female patients; median age 55 years) with spinal (cervical, n = 61; thoracic, n = 29; lumbar, n = 13; sacral, n = 46; pelvic, n = 6) classic chordomas (n = 116) and chondrosarcomas (n = 39; most were low grade) were treated with maximal safe resection followed by PBS-PT (median dose prescribed: 74 Gy [relative biological effectiveness], range 48.6-77 Gy). The majority of patients (n = 153, 98.7%) had undergone at least 1 resection prior to PBS-PT (median 1, range 0-5; biopsy only, n = 2). Fewer than half (45.1%) of the surgeries were rated as gross-total resections (GTRs) prior to PBS-PT. Surgical stabilization (SS) was present in 39% of all patients (n = 60). Ninety-one patients (59%) presented with macroscopic tumor at the start of PBS-PT. The median follow-up duration was 64.7 months (range 12.2-204.8 months).

Results: The 5-year local tumor control, disease-free survival (DFS), and overall survival were 64.9% (95% CI 56.3%-73.5%), 59.4% (95% CI 50.6%-68.2%), and 77.9% (95% CI 70.6%-85.2%), respectively. In total, 63 patients (40.6%) experienced failure during the follow-up period: local only in 32 (20.6%), distal only in 7 (4.5%), local + distal in 19 (12.3%), surgical pathway failure (SPF) only in 2 (1.3%), local + SPF in 2 (1.3%), and distal + SPF in 1 (< 1%). Univariate analysis identified gross residual disease, the presence of SS, and treatment era prior to 2008 as highly significant for worse outcome, with all 3 remaining significant on multivariate analysis. The type of surgery (GTR or subtotal resection/biopsy) and whether GTR was achieved by en bloc or curettage did not show a significant prognostic effect. Surgical complications prior to PBS-PT were present in 42.5% of all surgically treated patients and were seen more commonly in patients with multiple surgical interventions (p = 0.005) and those operated on with the intent of en bloc resection (p = 0.006).

Conclusions: The extent of resection and metallic stabilization substantially influenced clinical outcomes for patients with spinal chordoma or chondrosarcoma despite high-dose adjuvant PBS-PT. Optimal upfront surgical management of these tumors continues to include GTR, as possible, with prompt adjuvant proton therapy.
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http://dx.doi.org/10.3171/2019.11.SPINE1927DOI Listing
January 2020

Pitfalls in the beam modelling process of Monte Carlo calculations for proton pencil beam scanning.

Br J Radiol 2020 Mar 6;93(1107):20190919. Epub 2020 Feb 6.

Centre for Proton Therapy, Paul Scherrer Institute, Villigen, Switzerland.

Objective: Monte Carlo (MC) simulations substantially improve the accuracy of predicted doses. This study aims to determine and quantify the uncertainties of setting up such a MC system.

Methods: Doses simulated with two Geant4-based MC calculation codes, but tuned to the beam data, have been compared. Different methods of MC modelling of a pre-absorber have been employed, either modifying the beam source parameters (descriptive) or adding the pre-absorber as a physical component (physical).

Results: After the independent beam modelling of both systems in water (resulting in excellent range agreement) range differences of up to 3.6/4.8 mm (1.5% of total range) in bone/brain-like tissues were found, which resulted from the use of different mean water ionisation potentials during the energy tuning process. When repeating using a common definition of water, ranges in bone/brain agreed within 0.1 mm and gamma-analysis (global 1%,1mm) showed excellent agreement (>93%) for all patient fields. However, due to a lack of modelling of proton fluence loss in the descriptive pre-absorber, differences of 7% in absolute dose between the pre-absorber definitions were found.

Conclusion: This study quantifies the influence of using different water ionisation potentials during the MC beam modelling process. Furthermore, when using a descriptive pre-absorber model, additional Faraday cup or ionisation chamber measurements with pre-absorber are necessary.

Advances In Knowledge: This is the first study quantifying the uncertainties caused by the MC beam modelling process for proton pencil beam scanning, and a more detailed beam modelling process for MC simulations is proposed to minimise the influence of critical parameters.
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http://dx.doi.org/10.1259/bjr.20190919DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7066947PMC
March 2020

Benchmarking a commercial proton therapy solution: The Paul Scherrer Institut experience.

Br J Radiol 2020 Mar 30;93(1107):20190920. Epub 2020 Jan 30.

Zentrum für Protonentherapie, Paul Scherrer Institut, Villigen, Switzerland.

Objective: For the past 20 years, Paul Scherrer Institut (PSI) has treated more than 1500 patients with deep-seated tumors using PSI-Plan, an in-house developed treatment planning system (TPS) used for proton beam scanning proton therapy, in combination with its home-built gantries. The goal of the present work is to benchmark the performance of a new TPS/Gantry system for proton therapy centers which have established already a baseline standard of care.

Methods And Materials: A total of 31 cases (=52 plans) distributed around 7 anatomical sites and 12 indications were randomly selected and re-planned using Eclipse™. The resulting plans were compared with plans formerly optimized in PSI-Plan, in terms of target coverage, plan quality, organ-at-risk (OAR) sparing and number of delivered pencil beams.

Results: Our results show an improvement on target coverage and homogeneity when using Eclipse™ while PSI-Plan showed superior plan conformity. As for OAR sparing, both TPS achieved the clinical constraints. The number of pencil beams required per plan was on average 3.4 times higher for PSI-Plan.

Conclusion: Both systems showed a good capacity to produce satisfactory plans, with Eclipse™ being able to achieve better target coverage and plan homogeneity without compromising OARs.

Advances In Knowledge: A benchmark between a clinically tested and validated system with a commercial solution is of interest for emerging proton therapy, equipped with commercial systems and no previous experience with proton beam scanning.
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http://dx.doi.org/10.1259/bjr.20190920DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7066977PMC
March 2020

Combination of Proton Therapy and Radionuclide Therapy in Mice: Preclinical Pilot Study at the Paul Scherrer Institute.

Pharmaceutics 2019 Sep 2;11(9). Epub 2019 Sep 2.

Center for Proton Therapy, Paul Scherrer Institute, 5232 Villigen-PSI, Switzerland.

Proton therapy (PT) is a treatment with high dose conformality that delivers a highly-focused radiation dose to solid tumors. Targeted radionuclide therapy (TRT), on the other hand, is a systemic radiation therapy, which makes use of intravenously-applied radioconjugates. In this project, it was aimed to perform an initial dose-searching study for the combination of these treatment modalities in a preclinical setting. Therapy studies were performed with xenograft mouse models of folate receptor (FR)-positive KB and prostate-specific membrane antigen (PSMA)-positive PC-3 PIP tumors, respectively. PT and TRT using Lu-folate and Lu-PSMA-617, respectively, were applied either as single treatments or in combination. Monitoring of the mice over nine weeks revealed a similar tumor growth delay after PT and TRT, respectively, when equal tumor doses were delivered either by protons or by β¯-particles, respectively. Combining the methodologies to provide half-dose by either therapy approach resulted in equal (PC-3 PIP tumor model) or even slightly better therapy outcomes (KB tumor model). In separate experiments, preclinical positron emission tomography (PET) was performed to investigate tissue activation after proton irradiation of the tumor. The high-precision radiation delivery of PT was confirmed by the resulting PET images that accurately visualized the irradiated tumor tissue. In this study, the combination of PT and TRT resulted in an additive effect or a trend of synergistic effects, depending on the type of tumor xenograft. This study laid the foundation for future research regarding therapy options in the situation of metastasized solid tumors, where surgery or PT alone are not a solution but may profit from combination with systemic radiation therapy.
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http://dx.doi.org/10.3390/pharmaceutics11090450DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6781294PMC
September 2019

Intensity modulated proton therapy plan generation in under ten seconds.

Acta Oncol 2019 Oct 4;58(10):1435-1439. Epub 2019 Jul 4.

Center for Proton Therapy, Paul Scherrer Institute , Villigen , Switzerland.

Treatment planning for intensity modulated proton therapy (IMPT) can be significantly improved by reducing the time for plan calculation, facilitating efficient sampling of the large solution space characteristic of IMPT treatments. Additionally, fast plan generation is a key for online adaptive treatments, where the adapted plan needs to be ideally available in a few seconds. However, plan generation is a computationally demanding task and, although dose restoration methods for adaptive therapy have been proposed, computation times remain problematic. IMPT plan generation times were reduced by the development of dedicated graphical processing unit (GPU) kernels for our in-house, clinically validated, dose and optimization algorithms. The kernels were implemented into a coherent system, which performed all steps required for a complete treatment plan generation. Using a single GPU, our fast implementation was able to generate a complete new treatment plan in 5-10 sec for typical IMPT cases, and in under 25 sec for plans to very large volumes such as for cranio-spinal axis irradiations. Although these times did not include the manual input of optimization parameters or a final clinical dose calculation, they included all required computational steps, including reading of CT and beam data. In addition, no compromise was made on plan quality. Target coverage and homogeneity for four patient plans improved (by up to 6%) or remained the same (changes <1%). No worsening of dose-volume parameters of the relevant organs at risk by more than 0.5% was observed. Fast plan generation with a clinically validated dose calculation and optimizer is a promising approach for daily adaptive proton therapy, as well as for automated or highly interactive planning.
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http://dx.doi.org/10.1080/0284186X.2019.1630753DOI Listing
October 2019

Results of a multicentre dosimetry audit using a respiratory phantom within the EORTC LungTech trial.

Radiother Oncol 2019 09 25;138:106-113. Epub 2019 Jun 25.

Department of Radiation Oncology, Catharina Hospital, Eindhoven, The Netherlands. Electronic address:

Introduction: The EORTC 22113-08113 LungTech trial assesses the safety and efficacy of SBRT for centrally located NSCLC. To insure protocol compliance an extensive RTQA procedure was implemented.

Methods: Twelve centres were audited using a CIRS008A phantom. The phantom was scanned using target inserts of 7.5 mm and 12.5 mm radius in static condition. For the 7.5 mm insert a 4DCT was acquired while moving according to a cos function. Treatment plans were measured using film and an ionization chamber. Wilcoxon's signed-rank tests were performed to compare the three plans across institutions. A Spearman correlation was calculated to evaluate the influence of factors such as PTV, slice thickness and total number of monitor units on the dosimetric results.

Results: The reference output dose median [min, max] variation was 0.5% [-1.1, +1.5]. The median deviations between chamber doses and point-planned doses were 1.8% [-0.1; 6.7] for the 7.5 mm and 1.1% [-2.8; 5.0] for the 12.5 mm sphere in static situation and 3.2% [-3.2; 15.7] for the dynamic situation. Film gamma median pass rates were 92.0% [68.0, 99.0] for 7.5 mm static, 96.2% [73.0, 99.0] for 12.5 mm static and 71.0% [40.0, 99.0] for 7.5 mm dynamic. Wilcoxon's signed-rank tests showed that the dynamic irradiations resulted in significantly lower gamma pass rates compared to the 12.5 mm static plan (p = 0.001). The total number of MUs per plan was correlated to both film and IC results.

Conclusion: An end-to-end audit was successfully performed, revealing important variations between institutions especially in dynamic irradiations. This shows the importance of dosimetry audits and the potentials for further technique and methodology improvements.
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http://dx.doi.org/10.1016/j.radonc.2019.06.008DOI Listing
September 2019

Bringing Europe together in building clinical evidence for proton therapy - the EPTN-ESTRO-EORTC endeavor.

Acta Oncol 2019 10 26;58(10):1340-1342. Epub 2019 Jun 26.

Department of Radiation Oncology, Ghent University Hospital and Ghent University , Ghent , Belgium.

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http://dx.doi.org/10.1080/0284186X.2019.1624820DOI Listing
October 2019

Towards FLASH proton therapy: the impact of treatment planning and machine characteristics on achievable dose rates.

Acta Oncol 2019 Oct 26;58(10):1463-1469. Epub 2019 Jun 26.

Center for Proton Therapy, Paul Scherrer Institute , Villigen , Switzerland.

This study aimed at evaluating spatially varying instantaneous dose rates for different intensity-modulated proton therapy (IMPT) planning strategies and delivery scenarios, and comparing these with FLASH dose rates (>40 Gy/s). In order to quantify dose rates in three-dimensions, we proposed the 'dose-averaged dose rate' (DADR) metric, defined for each voxel as the dose-weighted mean of the instantaneous dose rates of all spots (i.e., pencil beams). This concept was applied to four head-and-neck cases, each planned with clinical (4 fields) and various spot-reduced IMPT techniques: 'standard' (4 fields), 'arc' (120 fields) and 'arc-shoot-through' (120 fields; 229 MeV only). For all plans, different delivery scenarios were simulated: constant beam intensity, variable beam intensity for a clinical Varian ProBeam system, varied per energy layer or per spot, and theoretical spot-wise variable beam intensity (i.e., no monitor/safety limitations). DADR distributions were calculated assuming 2-Gy or 6-Gy fractions. Spot-reduced plans contained 17-52 times fewer spots than clinical plans, with no deterioration of plan quality. For the clinical plans, the mean DADR in normal tissue for 2-Gy fractionation was 1.7 Gy/s (median over all patients) at maximum, whereas in standard spot-reduced plans it was 0.7, 4.4, 7.1, and 12.1 Gy/s, for the constant, energy-layer-wise, spot-wise, and theoretical spot-wise delivery scenarios, respectively. Similar values were observed for arc plans. Arc-shoot-through planning resulted in DADR values of 3.0, 6.0, 14.1, and 24.4 Gy/s, for the abovementioned scenarios. Hypofractionation (3×) generally resulted in higher dose rates, up to 73.2 Gy/s for arc-shoot-through plans. The DADR was inhomogeneously distributed with highest values at beam entrance and at the Bragg peak. FLASH dose rates were not achieved for conventional planning and clinical spot-scanning machines. As such, increased spot-wise beam intensities, spot-reduced planning, hypofractionation and arc-shoot-through plans were required to achieve FLASH compatible dose rates.
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http://dx.doi.org/10.1080/0284186X.2019.1627416DOI Listing
October 2019

Proton therapy for brain tumours in the area of evidence-based medicine.

Br J Radiol 2020 Mar 20;93(1107):20190237. Epub 2019 May 20.

Center for Proton Therapy, Paul Scherrer Institute, Villigen, Switzerland.

Advances In Knowledge: This review details the indication of brain tumors for proton therapy and give a list of the open prospective trials for these challenging tumors.
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http://dx.doi.org/10.1259/bjr.20190237DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7066950PMC
March 2020

Dosimetric uncertainties as a result of temporal resolution in 4D dose calculations for PBS proton therapy.

Phys Med Biol 2019 06 13;64(12):125005. Epub 2019 Jun 13.

Center for Proton Therapy, Paul Scherrer Institut, Villigen-PSI, Switzerland. Author to whom any correspondence should be addressed.

This work investigates the dosimetric impact on 4D dose distribution estimation for pencil beam scanned (PBS) proton therapy as function of the temporal resolution used for the time resolved dose calculation. For three liver patients (CTV volume: 403/122/264 cc), 10-phase 4DCT-MRI datasets with ~15 mm tumour motion were simulated for seven different motion periods (2-8 s). 4D dose distributions were calculated and compared by considering both coarser and finer temporal resolutions (200-800 ms and 20 ms). Single scanned 4D plans for seven fraction doses (0.7/2/4/6/8/10/12 Gy) were investigated, whose dose delivery timelines were simulated by assuming two types of PBS scanning modes: (1) layer-wise raster scanning with varying dose rate per layer and (2) fixed dose rate, discrete scanning. For both delivery scenarios, dosimetric assessments were performed by comparing corresponding dose distributions derived from the two 4D dose calculation (4DDC) results. Differences were quantified as the difference in D5-D95 of the CTV and by comparing total volume of the CTV receiving point-to-point absolute dose difference more than 5%. Our results show that varying temporal resolution in 4DDC has a direct influence on the final accumulated dose distribution. For all scenarios, patients, fraction doses and motion periods studied, pronounced dose differences can be observed between the two 4DDC results. However, the magnitude of differences varies depending on the selected PBS scanning model and prescribed dose per field. For fixed dose rate delivery, the average duration of the delivery of each spot increases for hypo-fractionated treatments, enhancing the benefit of using a finer temporal resolution for 4DDC. In particular, for fraction doses  >4 Gy and motion periods less than 4 s, warping the dose between discrete 4DCT phases can over predict the interplay effect (D5-D95 in CTV) by 3%-10% compared to the use of a finer temporal resolution, resulting in more than 20% of CTV voxels having absolute dose differences of over 5% between the two 4DDC approaches. These findings emphasize the importance for PBS 4DDC using finer temporal resolutions than provided by conventional 4D dose accumulation techniques. In particular, the observed differences in dosimetric effects using the fine temporal resolution provided by dose warping cannot be neglected for hypo-fractionation and short breathing periods, especially when using constant dose rates for dose delivery.
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http://dx.doi.org/10.1088/1361-6560/ab1d6fDOI Listing
June 2019

The dosimetric effect of residual breath-hold motion in pencil beam scanned proton therapy - An experimental study.

Radiother Oncol 2019 05 14;134:135-142. Epub 2019 Feb 14.

Paul Scherrer Institute, ETH Domain, Switzerland.

Background And Purpose: Motion management in the treatment of lung cancer is necessary to assure highest quality of the delivered radiation therapy. In this study, the breath-hold technique is experimentally investigated for pencil beam scanned (PBS) proton therapy, with respect to the dosimetric effect of residual breath-hold motion.

Material And Methods: Three-dimensional (3D)-printed tumours extracted from CT scans of three patients were inserted into a dynamic anthropomorphic breathing phantom. The target was set up to move with the individual patient's tumour motion during breath-hold as previously assessed on fluoroscopy. Target dose was measured with radio-chromic film, and both single field uniform dose (SFUD) and intensity-modulated proton therapy (IMPT) plans were delivered. Experiments were repeated for each patient without any motion, to compute the relative dose deviation between static and breath-hold cases.

Results: SFUD plans showed small dose deviations between static and breath-hold cases, as evidenced by the gamma pass rate (3%, 3 mm) of 85% or higher. Dose deviation was more evident for IMPT plans, with gamma pass rate reduced to 50-70%.

Conclusions: The breath-hold technique is robust to residual intra-breath-hold motion for SFUD treatment plans, based on our experimental study. IMPT was less robust with larger detected dose deviations.
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http://dx.doi.org/10.1016/j.radonc.2019.01.033DOI Listing
May 2019

Early results and volumetric analysis after spot-scanning proton therapy with concomitant hyperthermia in large inoperable sacral chordomas.

Br J Radiol 2020 Mar 14;93(1107):20180883. Epub 2019 May 14.

Center for Proton Therapy, Paul Scherrer Institute, ETH Domain, Villigen PSI, Switzerland.

Objective: Large inoperable sacral chordomas show unsatisfactory local control rates even when treated with high dose proton therapy (PT). The aim of this study is assessing feasibility and reporting early results of patients treated with PT and concomitant hyperthermia (HT).

Methods: : Patients had histologically proven unresectable sacral chordomas and received 70 Gy (relative biological effectiveness) in 2.5 Gy fractions with concomitant weekly HT. Toxicity was assessed according to CTCAE_v4. A volumetric tumor response analysis was performed.

Results: : Five patients were treated with the combined approach. Median baseline tumor volume was 735 cc (range, 369-1142). All patients completed PT and received a median of 5 HT sessions (range, 2-6). Median follow-up was 18 months (range, 9-26). The volumetric analysis showed an objective response of all tumors (median shrinkage 46%; range, 9-72). All patients experienced acute Grade 2-3 local pain. One patient presented with a late Grade 3 iliac fracture.

Conclusion: Combining PT and HT in large inoperable sacral chordomas is feasible and causes acceptable toxicity. Volumetric analysis shows promising early results, warranting confirmation in the framework of a prospective trial.

Advances In Knowledge: : This is an encouraging first report of the feasibility and early results of concomitant HT and PT in treating inoperable sacral chordoma.
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http://dx.doi.org/10.1259/bjr.20180883DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7066944PMC
March 2020