A planning study of proton therapy dose escalation for non-small cell lung cancer.

In non-small-cell lung cancer (NSCLC), improving local control through radiotherapy dose escalation might improve survival. However, a photon-based RCT showed increased organ at risk dose exposure and worse overall survival in the dose escalation arm. In this study, intensity-modulated proton therapy plans with dose escalation to the primary tumour were created for 20 NSCLC patients.

Dose evaluation of inter- and intra-fraction prostate motion in extremely hypofractionated intensity-modulated proton therapy for prostate cancer.

Inter- and intra-fractional prostate motion can deteriorate the dose distribution in extremely hypofractionated intensity-modulated proton therapy. We used verification CTs and prostate motion data calculated from 1024 intra-fractional prostate motion records to develop a voxel-wise based 4-dimensional method, which had a time resolution of 1 s, to assess the dose impact of prostate motion. An example of 100 fractional simulations revealed that motion had minimal impact on planning dose, the accumulated dose in 95 % of the scenarios fulfilled the clinical goals for target coverage (D95 > 37.

Partitioning of discrete proton arcs into interlaced subplans can bring proton arc advances to existing proton facilities.

Background: Proton arcs have shown potential to reduce the dose to organs at risks (OARs) by delivering the protons from many different directions. While most previous studies have been focused on dynamic arcs (delivery during rotation), an alternative approach is discrete arcs, where step-and-shoot delivery is used over a large number of beam directions. The major advantage of discrete arcs is that they can be delivered at existing proton facilities.

Proton arc therapy increases the benefit of proton therapy for oropharyngeal cancer patients in the model based clinic.

Background And Purpose: In the model-based approach, patients qualify for proton therapy when the reduction in risk of toxicity (ΔNTCP) obtained with IMPT relative to VMAT is larger than predefined thresholds as defined by the Dutch National Indication Protocol (NIPP). Proton arc therapy (PAT) is an emerging technology which has the potential to further decrease NTCPs compared to IMPT. The aim of this study was to investigate the potential impact of PAT on the number of oropharyngeal cancer (OPC) patients that qualify for proton therapy.

Clinical 3D/4D cumulative proton dose assessment methods for thoracic tumours with large motion.

Purpose: Despite the anticipated clinical benefits of intensity-modulated proton therapy (IMPT), plan robustness may be compromised due to its sensitivity to patient treatment uncertainties, especially for tumours with large motion. In this study, we investigated treatment course-wise plan robustness for intra-thoracic tumours with large motion comparing a 4D pre-clinical evaluation method (4DREM) to our clinical 3D/4D dose reconstruction and accumulation methods.

Materials And Methods: Twenty patients with large target motion (>10 mm) were treated with five times layered rescanned IMPT.

Automated Robust Planning for IMPT in Oropharyngeal Cancer Patients Using Machine Learning.

Purpose: The aim of this study was to evaluate an automated treatment planning method for robustly optimized intensity modulated proton therapy (IMPT) plans for oropharyngeal carcinoma patients and to compare the results with manually optimized robust IMPT plans.

Methods And Materials: An atlas regression forest-based machine learning (ML) model for dose prediction was trained on CT scans, contours, and dose distributions of robust IMPT plans of 88 oropharyngeal cancer (OPC) patients. The ML model was combined with a robust voxel and dose volume histogram-based dose mimicking optimization algorithm for 21 perturbed scenarios to generate a machine-deliverable plan from the predicted dose distribution.

Spot scanning proton arc therapy reduces toxicity in oropharyngeal cancer patients.

Background: Proton arc technology has recently shown dosimetric gains for various treatment indications. The increased number of beams and energy layers (ELs) in proton arc plans, increases the degrees of freedom in plan optimization and thereby flexibility to spare dose in organs at risk (OARs). A relationship exists between dosimetric plan quality, delivery efficiency, the number of ELs -and beams in a proton arc plan.

Robustness assessment of clinical adaptive proton and photon radiotherapy for oesophageal cancer in the model-based approach.

Purpose: In the Netherlands, oesophageal cancer (EC) patients are selected for intensity modulated proton therapy (IMPT) using the expected normal tissue complication probability reduction (ΔNTCP) when treating with IMPT compared to volumetric modulated arc therapy (VMAT). In this study, we evaluate the robustness of the first EC patients treated with IMPT in our clinic in terms of target and organs-at-risk (OAR) dose with corresponding NTCP, as compared to VMAT.

Materials And Methods: For 20 consecutive EC patients, clinical IMPT and VMAT plans were created on the average planning 4DCT.

Treatment planning comparison in the PROTECT-trial randomising proton versus photon beam therapy in oesophageal cancer: Results from eight European centres.

Purpose: To compare dose distributions and robustness in treatment plans from eight European centres in preparation for the European randomized phase-III PROTECT-trial investigating the effect of proton therapy (PT) versus photon therapy (XT) for oesophageal cancer.

Materials And Methods: All centres optimized one PT and one XT nominal plan using delineated 4DCT scans for four patients receiving 50.4 Gy (RBE) in 28 fractions.

Diaphragm-Based Position Verification to Improve Daily Target Dose Coverage in Proton and Photon Radiation Therapy Treatment of Distal Esophageal Cancer.

Purpose: In modern conformal radiation therapy of distal esophageal cancer, target coverage can be affected by variations in the diaphragm position. We investigated if daily position verification (PV) extended by a diaphragm position correction would optimize target dose coverage for esophageal cancer treatment.

Methods And Materials: For 15 esophageal cancer patients, intensity modulated proton therapy (IMPT) and volumetric modulated arc therapy (VMAT) plans were computed.

Assessment of a diaphragm override strategy for robustly optimized proton therapy planning for esophageal cancer patients.

Purpose: To ensure target coverage in the treatment of esophageal cancer, a density override to the region of diaphragm motion can be applied in the optimization process. Here, we evaluate the benefit of this approach during robust optimization for intensity modulated proton therapy (IMPT) planning.

Materials And Methods: For 10 esophageal cancer patients, two robustly optimized IMPT plans were created either using (WDO) or not using (NDO) a diaphragm density override of 1.

Quality of life and toxicity guided treatment plan optimisation for head and neck cancer.

Purpose: To evaluate the feasibility of semi-automatic Quality of Life (QOL)-weighted normal tissue complication probability (NTCP)-guided VMAT treatment plan optimisation in head and neck cancer (HNC) and compare predicted QOL to that obtained with conventional treatment.

Materials And Methods: This study included 30 HNC patients who were treated with definitive radiotherapy. QOL-weighted NTCP-guided VMAT plans were optimised directly on 80 multivariable NTCP models of 20 common toxicities and symptoms on 4 different time points (6, 12, 18 and 24 months after radiotherapy) and each NTCP model was weighted relative to its impact on QOL.

Towards the clinical implementation of intensity-modulated proton therapy for thoracic indications with moderate motion: Robust optimised plan evaluation by means of patient and machine specific information.

Purpose: Compared to volumetric modulated arc therapy (VMAT), clinical benefits are anticipated when treating thoracic tumours with intensity-modulated proton therapy (IMPT). However, the current concern of plan robustness as a result of motion hampers its wide clinical implementation. To define an optimal protocol to treat lung and oesophageal cancers, we present a comprehensive evaluation of IMPT planning strategies, based on patient 4DCTs and machine log files.

Head and neck IMPT probabilistic dose accumulation: Feasibility of a 2 mm setup uncertainty setting.

Objective: To establish optimal robust optimization uncertainty settings for clinical head and neck cancer (HNC) patients undergoing 3D image-guided pencil beam scanning (PBS) proton therapy.

Methods: We analyzed ten consecutive HNC patients treated with 70 and 54.25 Gy to the primary and prophylactic clinical target volumes (CTV) respectively using intensity-modulated proton therapy (IMPT).

First experience with model-based selection of head and neck cancer patients for proton therapy.

Purpose: In the Netherlands, head and neck cancer (HNC) patients qualify for intensity modulated proton therapy (IMPT) based on model-based selection (MBS). The aim of this study was to evaluate the first experience in MBS of HNC patients.

Methods: Patients who were subjected to MBS (Jan 2018-Sep 2019) were evaluated.

Weekly robustness evaluation of intensity-modulated proton therapy for oesophageal cancer.

Background And Purpose: Intensity-modulated proton therapy (IMPT) is expected to result in clinical benefits by lowering radiation dose to organs-at-risk (OARs). However, there are concerns about plan robustness due to motion. To address this uncertainty we evaluated the robustness of IMPT compared to the widely clinically used volumetric modulated arc therapy (VMAT) on weekly repeated computed tomographies (CT).

Organ sparing potential and inter-fraction robustness of adaptive intensity modulated proton therapy for lung cancer.

The aim of this study was to compare adaptive intensity modulated proton therapy (IMPT) robustness and organ sparing capabilities with that of adaptive volumetric arc photon therapy (VMAT). Eighteen lung cancer patients underwent a planning 4DCT (p4DCT) and 5 weekly repeated 4DCT (r4DCT) scans. Target volumes and organs at risk were manually delineated on the three-dimensional (3D) average scans of the p4DCT (av_p4DCT) and of the r4DCT scans (av_r4DCT).

Practical robustness evaluation in radiotherapy - A photon and proton-proof alternative to PTV-based plan evaluation.

Background And Purpose: A planning target volume (PTV) in photon treatments aims to ensure that the clinical target volume (CTV) receives adequate dose despite treatment uncertainties. The underlying static dose cloud approximation (the assumption that the dose distribution is invariant to errors) is problematic in intensity modulated proton treatments where range errors should be taken into account as well. The purpose of this work is to introduce a robustness evaluation method that is applicable to photon and proton treatments and is consistent with (historic) PTV-based treatment plan evaluations.

Evaluating the benefit of PBS vs. VMAT dose distributions in terms of dosimetric sparing and robustness against inter-fraction anatomical changes for pediatric abdominal tumors.

Background And Purpose: To evaluate the dosimetric sparing and robustness against inter-fraction anatomical changes between photon and proton dose distributions for children with abdominal tumors.

Material And Methods: Volumetric modulated arc therapy (VMAT) and intensity-modulated pencil beam scanning (PBS) proton dose distributions were calculated for 20 abdominal pediatric cases (average 3, range 1-8 years). VMAT plans were based on a full-arc while PBS plans on 2-3 posterior-oblique irradiation fields.

Composite minimax robust optimization of VMAT improves target coverage and reduces non-target dose in head and neck cancer patients.

Background And Purpose: To assess the potential of composite minimax robust optimization (CMRO) compared to planning target volume (PTV)-based optimization for head and neck cancer (HNC) patients treated with volumetric modulated arc therapy (VMAT).

Materials And Methods: Ten HNC patients previously treated with a PTV-based VMAT plan were studied. In addition to the PTV-plan a VMAT plan was created with CMRO.

Comprehensive 4D robustness evaluation for pencil beam scanned proton plans.

Due to anticipated clinical benefits, moving targets are potential future indications for pencil beam scanned proton therapy (PBS-PT). However, currently they are not widely treated at PBS-PT facilities due to dosimetric uncertainties caused by motion. We developed a method, the 4D robustness evaluation method (4DREM), to realistically and efficiently assess all possible events impacting PBS-PT treatments in the thorax.

Feasibility of MRI-only photon and proton dose calculations for pediatric patients with abdominal tumors.

The purpose of this study was to develop a method enabling synthetic computed tomography (sCT) generation of the whole abdomen using magnetic resonance imaging (MRI) scans of pediatric patients with abdominal tumors. The proposed method relies on an automatic atlas-based segmentation of bone and lungs followed by an MRI intensity to synthetic Hounsfield unit conversion. Separate conversion algorithms were used for bone, lungs and soft-tissue.

Automated Robust Proton Planning Using Dose-Volume Histogram-Based Mimicking of the Photon Reference Dose and Reducing Organ at Risk Dose Optimization.

Purpose: Patient selection for proton therapy is increasingly based on proton to photon plan comparisons. To improve efficient decision making, we developed a dose mimicking and reducing (DMR) algorithm to automatically generate a robust proton plan from a reference photon dose, as well as target and organ at risk (OAR) delineations.

Methods And Materials: The DMR algorithm was evaluated in 40 patients with head and neck cancer.

Limited Impact of Setup and Range Uncertainties, Breathing Motion, and Interplay Effects in Robustly Optimized Intensity Modulated Proton Therapy for Stage III Non-small Cell Lung Cancer.

Purpose: To investigate the impact of setup and range uncertainties, breathing motion, and interplay effects using scanning pencil beams in robustly optimized intensity modulated proton therapy (IMPT) for stage III non-small cell lung cancer (NSCLC).

Methods And Materials: Three-field IMPT plans were created using a minimax robust optimization technique for 10 NSCLC patients. The plans accounted for 5- or 7-mm setup errors with ±3% range uncertainties.

Multivariable normal tissue complication probability model-based treatment plan optimization for grade 2-4 dysphagia and tube feeding dependence in head and neck radiotherapy.

Background And Purpose: Radiotherapy of the head and neck is challenged by the relatively large number of organs-at-risk close to the tumor. Biologically-oriented objective functions (OF) could optimally distribute the dose among the organs-at-risk. We aimed to explore OFs based on multivariable normal tissue complication probability (NTCP) models for grade 2-4 dysphagia (DYS) and tube feeding dependence (TFD).