Opportunities and limitations of multileaf collimator based intensity modulated proton therapy

The vast majority of proton therapy institutes employ passive scattering beamlines. Treatments are delivered by means of laterally and distally conformed homogeneous dose distributions for each beam direction by utilizing spread-out Bragg peaks and custom milled hardware. Most newly built proton facilities rely upon scanned proton beams to provide intensity modulated therapy (IMPT), improvements in treatment planning and delivery workflow. This thesis investigates the benefits of IMPT in fixed proton therapy beamlines and describes aspects of multileaf collimator (MLC) based IMPT delivery. We show that IMPT has the potential to increase the range of applications for fixed proton therapy beamlines. A method for sequencing intensity modulated treatment plans into a set of segments is presented and evaluated based on results obtained for a set of clinical situations. The resulting numbers of segments made delivery technically and logistically feasible. Neutron dose was found acceptable given a well optimized beamline. The dosimetric properties of one specific multileaf collimator were investigated experimentally and compared to custom milled apertures. Small differences were found, but those are clinically insignificant in the vast majority of clinical cases. Finally, an extensive set of measurements for accurate determination of the peak dose as a function of field size is described

Nuclear halo of a 177 MeV proton beam in water: theory, measurement and parameterization

The dose distribution of a monoenergetic pencil beam in water consists of an electromagnetic "core", a "halo" from charged nuclear secondaries, and a much larger "aura" from neutral secondaries. These regions overlap, but each has distinct spatial characteristics. We have measured the core/halo using a 177MeV test beam offset in a water tank. The beam monitor was a fluence calibrated plane parallel ionization chamber (IC) and the field chamber, a dose calibrated Exradin T1, so the dose measurements are absolute (MeV/g/p). We performed depth-dose scans at ten displacements from the beam axis ranging from 0 to 10cm. The dose spans five orders of magnitude, and the transition from halo to aura is clearly visible. We have performed model-dependent (MD) and model-independent (MI) fits to the data. The MD fit separates the dose into core, elastic/inelastic nuclear, nonelastic nuclear and aura terms, and achieves a global rms measurement/fit ratio of 15%. The MI fit uses cubic splines and the same ratio is 9%. We review the literature, in particular the use of Pedroni's parametrization of the core/halo. Several papers improve on his Gaussian transverse distribution of the halo, but all retain his T(w), the radial integral of the depth-dose multiplying both the core and halo terms and motivating measurements with large "Bragg peak chambers" (BPCs). We argue that this use of T(w), which by its definition includes energy deposition by nuclear secondaries, is incorrect. T(w) should be replaced in the core term, and in at least part of the halo, by a purely electromagnetic mass stopping power. BPC measurements are unnecessary, and irrelevant to parameterizing the pencil beam.Comment: 55 pages, 4 tables, 29 figure

Immobilization precision of a modified GTC frame

The purpose of this study was to evaluate and quantify the interfraction reproducibility and intrafraction immobilization precision of a modified GTC frame. The error of the patient alignment and imaging systems were measured using a cranial skull phantom, with simulated, predetermined shifts. The kV setup images were acquired with a room‐mounted set of kV sources and panels. Calculated translations and rotations provided by the computer alignment software relying upon three implanted fiducials were compared to the known shifts, and the accuracy of the imaging and positioning systems was calculated. Orthogonal kV setup images for 45 proton SRT patients and 1002 fractions (average 22.3 fractions/patient) were analyzed for interfraction and intrafraction immobilization precision using a modified GTC frame. The modified frame employs a radiotransparent carbon cup and molded pillow to allow for more treatment angles from posterior directions for cranial lesions. Patients and the phantom were aligned with three 1.5 mm stainless steel fiducials implanted into the skull. The accuracy and variance of the patient positioning and imaging systems were measured to be 0.10±0.06 mm, with the maximum uncertainty of rotation being ±0.07°.957 pairs of interfraction image sets and 974 intrafraction image sets were analyzed. 3D translations and rotations were recorded. The 3D vector interfraction setup reproducibility was 0.13 mm ±1.8 mm for translations and the largest uncertainty of ±1.07° for rotations. The intrafraction immobilization efficacy was 0.19 mm ±0.66 mm for translations and the largest uncertainty of ±0.50° for rotations. The modified GTC frame provides reproducible setup and effective intrafraction immobilization, while allowing for the complete range of entrance angles from the posterior direction. PACS number: 87.53.Ly, 87.55.Q

Monitoring proton radiation therapy with in-room PET imaging

We used a mobile positron emission tomography (PET) scanner positioned within the proton therapy treatment room to study the feasibility of proton range verification with an in-room, stand-alone PET system, and compared with off-line equivalent studies. Two subjects with adenoid cystic carcinoma were enrolled into a pilot study in which in-room PET scans were acquired in list-mode after a routine fractionated treatment session. The list-mode PET data were reconstructed with different time schemes to generate in-room short, in-room long and off-line equivalent (by skipping coincidences from the first 15 min during the list-mode reconstruction) PET images for comparison in activity distribution patterns. A phantom study was followed to evaluate the accuracy of range verification for different reconstruction time schemes quantitatively. The in-room PET has a higher sensitivity compared to the off-line modality so that the PET acquisition time can be greatly reduced from 30 to <5 min. Features in deep-site, soft-tissue regions were better retained with in-room short PET acquisitions because of the collection of (15)O component and lower biological washout. For soft tissue-equivalent material, the distal fall-off edge of an in-room short acquisition is deeper compared to an off-line equivalent scan, indicating a better coverage of the high-dose end of the beam. In-room PET is a promising low cost, high sensitivity modality for the in vivo verification of proton therapy. Better accuracy in Monte Carlo predictions, especially for biological decay modeling, is necessary.Peer reviewe

Accuracy of proton beam range verification using post-treatment positron emission tomography/computed tomography as function of treatment site

PURPOSE: For 23 patients, an off-line positron emission tomography scan and a computed tomography scan after proton radiotherapy was performed at the Massachusetts General Hospital to assess in vivo treatment verification. A well-balanced population of patients was investigated to assess the effect of the tumor location on the accuracy of the technique. METHODS AND MATERIALS: Range verification was achieved by comparing the measured positron emission tomography activity distributions with the corresponding Monte Carlo-simulated distributions. Observed differences in the distal end of the activity distributions were analyzed as potential indicators for the range differences between the actual delivered and planned dose. RESULTS: The average spatial agreement between the measured and simulated activity distribution was within ±3 mm, and the corresponding average absolute agreement was within ±45% (derived from gamma index analysis). The mean absolute range deviation at 93 randomly chosen positions in 17 treatment fields delivered to 11 patients was 3.6 mm. Characteristic differences in the agreement of the measured and simulated activity distribution for the different tumor/target sites were found. This resulted from the different effect of factors such as biologic washout effects, motion, or limitations in the Monte Carlo-simulated activity patterns. CONCLUSION: We found that intracranial and cervical spine patients can greatly benefit from off-line positron emission tomography and computed tomography range verification. However, for the successful application of the method to patients with abdominopelvic tumors, major technological and methodologic improvements are needed. Among the intracranial and cervical spine target sites, patients with arteriovenous malformations or metal implants represent groups that could especially benefit from the approach

Immobilization precision of a modified GTC frame

The purpose of this study was to evaluate and quantify the interfraction reproducibility and intrafraction immobilization precision of a modified GTC frame. The error of the patient alignment and imaging systems were measured using a cranial skull phantom, with simulated, predetermined shifts. The kV setup images were acquired with a room-mounted set of kV sources and panels. Calculated translations and rotations provided by the computer alignment software relying upon three implanted fiducials were compared to the known shifts, and the accuracy of the imaging and positioning systems was calculated. Orthogonal kV setup images for 45 proton SRT patients and 1002 fractions (average 22.3 fractions/patient) were analyzed for interfraction and intrafraction immobilization precision using a modified GTC frame. The modified frame employs a radiotransparent carbon cup and molded pillow to allow for more treatment angles from posterior directions for cranial lesions. Patients and the phantom were aligned with three 1.5 mm stainless steel fiducials implanted into the skull. The accuracy and variance of the patient positioning and imaging systems were measured to be 0.10 +/- 0.06 mm, with the maximum uncertainty of rotation being +/- 0.07 degrees. 957 pairs of interfraction image sets and 974 intrafraction image sets were analyzed. 3D translations and rotations were recorded. The 3D vector interfraction setup reproducibility was 0.13 mm +/- 1.8 mm for translations and the largest uncertainty of +/- 1.07 degrees for rotations. The intrafraction immobilization efficacy was 0.19 mm +/- 0.66 mm for translations and the largest uncertainty of +/- 0.50 degrees for rotations. The modified GTC frame provides reproducible setup and effective intrafraction immobilization, while allowing for the complete range of entrance angles from the posterior directio

A survey of practice patterns for real-time intrafractional motion-management in particle therapy

Background and purpose: Organ motion compromises accurate particle therapy delivery. This study reports on the practice patterns for real-time intrafractional motion-management in particle therapy to evaluate current clinical practice and wishes and barriers to implementation. Materials and methods: An institutional questionnaire was distributed to particle therapy centres worldwide (7/2020–6/2021) asking which type(s) of real-time respiratory motion management (RRMM) methods were used, for which treatment sites, and what were the wishes and barriers to implementation. This was followed by a three-round DELPHI consensus analysis (10/2022) to define recommendations on required actions and future vision. With 70 responses from 17 countries, response rate was 100% for Europe (23/23 centres), 96% for Japan (22/23) and 53% for USA (20/38). Results: Of the 68 clinically operational centres, 85% used RRMM, with 41% using both rescanning and active methods. Sixty-four percent used active-RRMM for at least one treatment site, mostly with gating guided by an external marker. Forty-eight percent of active-RRMM users wished to expand or change their RRMM technique. The main barriers were technical limitations and limited resources. From the DELPHI analysis, optimisation of rescanning parameters, improvement of motion models, and pre-treatment 4D evaluation were unanimously considered clinically important future focus. 4D dose calculation was identified as the top requirement for future commercial treatment planning software. Conclusion:  A majority of particle therapy centres have implemented RRMM. Still, further development and clinical integration were desired by most centres. Joint industry, clinical and research efforts are needed to translate innovation into efficient workflows for broad-scale implementation

A survey of practice patterns for adaptive particle therapy for interfractional changes

Background and purpose: Anatomical changes may compromise the planned target coverage and organs-at-risk dose in particle therapy. This study reports on the practice patterns for adaptive particle therapy (APT) to evaluate current clinical practice and wishes and barriers to further implementation. Materials and methods: An institutional questionnaire was distributed to PT centres worldwide (7/2020–6/2021) asking which type of APT was used, details of the workflow, and what the wishes and barriers to implementation were. Seventy centres from 17 countries participated. A three-round Delphi consensus analysis (10/2022) among the authors followed to define recommendations on required actions and future vision. Results: Out of the 68 clinically operational centres, 84% were users of APT for at least one treatment site with head and neck being most common. APT was mostly performed offline with only two online APT users (plan-library). No centre used online daily re-planning. Daily 3D imaging was used for APT by 19% of users. Sixty-eight percent of users had plans to increase their use or change their technique for APT. The main barrier was “lack of integrated and efficient workflows”. Automation and speed, reliable dose deformation for dose accumulation and higher quality of in-room volumetric imaging were identified as the most urgent task for clinical implementation of online daily APT. Conclusion: Offline APT was implemented by the majority of PT centres. Joint efforts between industry research and clinics are needed to translate innovations into efficient and clinically feasible workflows for broad-scale implementation of online APT