Proton Therapy for Spinal Tumors: A Consensus Statement From the Particle Therapy Cooperative Group.

Purpose: Proton beam therapy (PBT) plays an important role in the management of primary spine tumors. The purpose of this consensus statement was to summarize safe and optimal delivery of PBT for spinal tumors.

Methods And Materials: The Particle Therapy Cooperative Group Skull Base/Central nervous system/Sarcoma Subcommittee consisting of radiation oncologists and medical physicists with specific expertise in spinal irradiation developed expert recommendations discussing treatment planning considerations and current approaches in the treatment of primary spinal tumors.

Multi-institutional experimental validation of online adaptive proton therapy workflows.

To experimentally validate two online adaptive proton therapy (APT) workflows using Gafchromic EBT3 films and optically stimulated luminescent dosimeters (OSLDs) in an anthropomorphic head-and-neck phantom.A three-field proton plan was optimized on the planning CT of the head-and-neck phantom with 2.0 Gy(RBE) per fraction prescribed to the clinical target volume.

Quantification of deformable image registration uncertainties for dose accumulation on head and neck cancer proton treatments.

Purpose: Head and neck cancer (HNC) patients in radiotherapy require adaptive treatment plans due to anatomical changes. Deformable image registration (DIR) is used in adaptive radiotherapy, e.g.

Optically stimulated luminescence dosimeters for simultaneous measurement of point dose and dose-weighted LET in an adaptive proton therapy workflow.

Purpose: To demonstrate the suitability of optically stimulated luminescence detectors (OSLDs) for accurate simultaneous measurement of the absolute point dose and dose-weighted linear energy transfer (LET) in an anthropomorphic phantom for experimental validation of daily adaptive proton therapy.

Methods: A clinically realistic intensity-modulated proton therapy (IMPT) treatment plan was created based on a CT of an anthropomorphic head-and-neck phantom made of tissue-equivalent material. The IMPT plan was optimized with three fields to deliver a uniform dose to the target volume covering the OSLDs.

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.

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.

Inter- and intrafractional 4D dose accumulation for evaluating ΔNTCP robustness in lung cancer.

Background And Purpose: Model-based selection of proton therapy patients relies on a predefined reduction in normal tissue complication probability (NTCP) with respect to photon therapy. The decision is necessarily made based on the treatment plan, but NTCP can be affected when the delivered treatment deviates from the plan due to delivery inaccuracies. Especially for proton therapy of lung cancer, this can be important because of tissue density changes and, with pencil beam scanning, the interplay effect between the proton beam and breathing motion.

Experimental validation of daily adaptive proton therapy.

Anatomical changes during proton therapy require rapid treatment plan adaption to mitigate the associated dosimetric impact. This in turn requires a highly efficient workflow that minimizes the time between imaging and delivery. At the Paul Scherrer Institute, we have developed an online adaptive workflow, which is specifically designed for treatments in the skull-base/cranium, with the focus set on simplicity and minimizing changes to the conventional workflow.

An approach for estimating dosimetric uncertainties in deformable dose accumulation in pencil beam scanning proton therapy for lung cancer.

Deformable image registration (DIR) is an important component for dose accumulation and associated clinical outcome evaluation in radiotherapy. However, the resulting deformation vector field (DVF) is subject to unavoidable discrepancies when different algorithms are applied, leading to dosimetric uncertainties of the accumulated dose. We propose here an approach for proton therapy to estimate dosimetric uncertainties as a consequence of modeled or estimated DVF uncertainties.

Dosimetric influence of deformable image registration uncertainties on propagated structures for online daily adaptive proton therapy of lung cancer patients.

Purpose: A major burden of introducing an online daily adaptive proton therapy (DAPT) workflow is the time and resources needed to correct the daily propagated contours. In this study, we evaluated the dosimetric impact of neglecting the online correction of the propagated contours in a DAPT workflow.

Material And Methods: For five NSCLC patients with nine repeated deep-inspiration breath-hold CTs, proton therapy plans were optimised on the planning CT to deliver 60 Gy-RBE in 30 fractions.

Extension of the phenotypic spectrum of GLE1-related disorders to a mild congenital form resembling congenital myopathy.

Background: GLE1 (GLE1, RNA Export Mediator, OMIM#603371) variants are associated with severe autosomal recessive motor neuron diseases, that are lethal congenital contracture syndrome 1 (LCCS1, OMIM#253310) and congenital arthrogryposis with anterior horn cell disease (CAAHD, OMIM#611890). The clinical spectrum of GLE1-related disorders has been expanding these past years, including with adult-onset amyotrophic lateral sclerosis (ALS) GLE1-related forms, especially through the new molecular diagnosis strategies associated with the emergence of next-generation sequencing (NGS) technologies. However, despite this phenotypic variability, reported congenital or ALS adult-onset forms remain severe, leading to premature death.

Deformable image registration uncertainty for inter-fractional dose accumulation of lung cancer proton therapy.

Background And Purpose: Non-small cell lung cancer (NSCLC) patients show typically large anatomical changes during treatment, making recalculation or adaption necessary. For report and review, the applied treatment dose can be accumulated on the reference planning CT using deformable image registration (DIR). We investigated the dosimetric impact of using six different clinically available DIR algorithms for dose accumulation in presence of inter-fractional anatomy variations.

Daily Adaptive Proton Therapy: Is it Appropriate to Use Analytical Dose Calculations for Plan Adaption?

Purpose: The accuracy of analytical dose calculations (ADC) and dose uncertainties resulting from anatomical changes are both limiting factors in proton therapy. For the latter, rapid plan adaption is necessary; for the former, Monte Carlo (MC) approaches are increasingly recommended. These, however, are inherently slower than analytical approaches, potentially limiting the ability to rapidly adapt plans.

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

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.

Online daily adaptive proton therapy.

It is recognized that the use of a single plan calculated on an image acquired some time before the treatment is generally insufficient to accurately represent the daily dose to the target and to the organs at risk. This is particularly true for protons, due to the physical finite range. Although this characteristic enables the generation of steep dose gradients, which is essential for highly conformal radiotherapy, it also tightens the dependency of the delivered dose to the range accuracy.

Daily adaptive proton therapy - the key to innovative planning approaches for paranasal cancer treatments.

For proton therapy of paranasal tumors, field directions avoiding volumes that might change during therapy are typically used. If the plan is optimized on the daily anatomy using daily adapted proton therapy (DAPT) however, field directions crossing the nasal cavities might be feasible. In this study, we investigated the effectiveness of DAPT for enabling narrow-field treatment approaches.

Radiation-induced optic neuropathy after pencil beam scanning proton therapy for skull-base and head and neck tumours.

Objective: To assess the radiation-induced optic neuropathy (RION) prevalence, following high dose pencil beam scanning proton therapy (PBSPT) to skull base and head and neck (H&N) tumours.

Methods: Between 1999 and 2014, 216 adult patients, median age 47 years (range, 18-77), were treated with PBS PT for skull base or H&N malignancies, delivering ≥45 Gy to the optic nerve(s) (ON) and/or optic chiasma (OC). The median administered dose to the planning target volume was 74.

Intensity modulated proton therapy plan generation in under ten seconds.

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.

Long term outcome of skull-base chondrosarcoma patients treated with high-dose proton therapy with or without conventional radiation therapy.

Background And Purpose: Skull-base chondrosarcoma (ChSa) is a rare bone tumor and the outcome of patients with this malignancy has been documented only in a limited number of series with a restricted number of patients.

Objective: This study was conducted to assess the outcome and prognostic factors of a large cohort of ChSa patients treated with radiotherapy in two proton therapy centers.

Materials And Methods: From 1996 to 2015, 251 (male, 43.

Long-Term Outcomes and Prognostic Factors After Pencil-Beam Scanning Proton Radiation Therapy for Spinal Chordomas: A Large, Single-Institution Cohort.

Purpose: To evaluate the efficacy and safety of high-dose pencil-beam scanning proton therapy (PBS-PT) in the adjuvant treatment of spinal chordomas.

Methods And Materials: Between 1997 and 2015, 100 patients with spinal chordomas (median age, 56 years; range, 25-81 years) were treated with adjuvant PBS-PT at the Paul Scherrer Institute: cervical (n = 46), thoracic (n = 4), lumbar (n = 12), and sacral (n = 38). The majority (88%) received PBS-PT alone rather than combined photon-proton therapy.

Anatomical robust optimization to account for nasal cavity filling variation during intensity-modulated proton therapy: a comparison with conventional and adaptive planning strategies.

The aim of this study is to develop an anatomical robust optimization method for intensity-modulated proton therapy (IMPT) that accounts for interfraction variations in nasal cavity filling, and to compare it with conventional single-field uniform dose (SFUD) optimization and online plan adaptation. We included CT data of five patients with tumors in the sinonasal region. Using the planning CT, we generated for each patient 25 'synthetic' CTs with varying nasal cavity filling.

A robust optimisation approach accounting for the effect of fractionation on setup uncertainties.

Proton plans are subject to a number of uncertainties which must be accounted for to ensure that they are delivered safely. Misalignment resulting from residual errors in daily patient positioning can result in both a displacement and distortion of dose distributions. This can be particularly important for intensity modulated proton therapy treatments where the accurate alignment of highly modulated fields may be required to deliver the intended treatment.

Clinical and Radiologic Outcomes in Adults and Children Treated with Pencil-Beam Scanning Proton Therapy for Low-Grade Glioma.

Purpose: We assessed clinical and radiologic outcomes in adults and children with low-grade glioma (LGG) of the brain treated with pencil-beam scanning (PBS) proton therapy (PT).

Materials And Methods: Between 1997 and 2014, 28 patients were treated with PBS PT, 20 (71%) of whom were younger than 18 years. Median age at start of PT was 12.

Effect of Anatomic Changes on Pencil Beam Scanned Proton Dose Distributions for Cranial and Extracranial Tumors.

Purpose: To estimate the frequency and impact of anatomic changes on the delivered dose in pencil beam scanning proton therapy, to assess the need for repeat CT scanning and adaptive replanning.

Methods And Materials: A total of 730 patients treated at Paul Scherrer Institut between 2007 and 2014 were included in this study, for which the number of patients who had control CT scans and who were replanned as a result of anatomic changes was analyzed. For those that were replanned, the nominal dose distributions (originally optimized on the planning CT scan) were recalculated on the replanning CT scan and differences evaluated using standard dose metrics for planning target volumes and clinical target volumes and organs at risk (OARs).

Long term outcomes of patients with skull-base low-grade chondrosarcoma and chordoma patients treated with pencil beam scanning proton therapy.

Purpose: To evaluate the long term tumor control and toxicity of skull base tumors treated with pencil beam scanning proton therapy (PT).

Materials And Methods: PT was delivered to 151 (68%) and 71 (32%) chordoma and chondrosarcoma (ChSa) patients, respectively. Mean age of patients was 40.