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. PURPOSE: This work aims to investigate the effect of the number of beams and ELs in a proton arc plan, on toxicity and delivery time for oropharyngeal cancer patients (OPC) selected for intensity modulated proton therapy (IMPT) based on the Dutch model-based approach. METHODS: The EL reduction algorithm iteratively selects ELs from beams equidistantly spaced over a 360° arc. The beams in the final plan may contain multiple ELs, making them suited for static delivery on the studied treatment machine. The produced plans can therefore be called "step and shoot" proton arc plans. The number of beams and ELs were varied to determine the relationship with the planning cost function value, normal tissue complication probability (NTCP) and delivery time. Proton arc plans with robust target coverage and optimal energy layer reduction (ELR) settings to reduce NTCP, were generated for 10 OPC patients. Proton arc plans were compared to clinical volumetric modulated arc therapy (VMAT) and IMPT plans in terms of integral dose, OAR dose, NTCP for xerostomia and dysphagia and delivery time. Furthermore, dose-weighted average linear energy transfer (LETd ) distributions were compared between the IMPT and proton arc plans. A dry run delivery of a plan containing 20 beams and 360 ELs was performed to evaluate delivery time and accuracy. RESULTS: We found 360 ELs distributed over 30 beams generated proton arc plans with near minimal expected plan toxicity. Relative to corresponding IMPT and VMAT plans, an average reduction of 21 ± 3% and 58 ± 10% in integral dose was observed. D m e a n $_{mean}$ was reduced most in the pharyngeal constrictor muscle (PCM) medius structure, with on average 9.0 ± 4.2 Gy(RBE) (p = 0.0002) compared to the clinical IMPT plans. The average NTCP for grade≥2 and grade≥3 xerostomia at 6 months after treatment significantly decreased with 4.7 ± 1.8% (p = 0.002) and 1.7 ± 0.8% (p = 0.002), respectively, while the average NTCP for grade≥2 and grade≥3 dysphagia decreased with 4.4 ± 2.9% (p = 0.002) and 0.9 ± 0.4% (p = 0.002), respectively, increasing the benefit of protons relative to VMAT. For a "step and shoot" proton arc delivery with auto beam sequencing the estimated delivery time is 11 min, similar to the delivery time of a 6-field IMPT treatment. Gamma analysis between the planned and delivered dose distribution resulted in a 99.99% pass rate using 1mm/1% dose difference/distance to agreement criteria. CONCLUSIONS: "Step and shoot" proton arc demonstrates potential to further reduce toxicity compared to IMPT and VMAT in OPC treatment. By employing 360 ELs and 30 beams in the proposed ELR method, delivery time can reach clinically acceptable levels without compromising plan toxicity when automatic beam sequencing is available.

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. MATERIALS AND METHODS: A prospective cohort of 223 OPC patients subjected to the model-based selection procedure was investigated. 33 (15%) patients were considered unsuitable for proton treatment before plan comparison. When IMPT was compared to VMAT for the remaining 190 patients, 148 (66%) patients qualified for protons and 42 (19%) patients did not. For these 42 patients treated with VMAT, robust PAT plans were generated. RESULTS: PAT plans provided better or similar target coverage compared to IMPT plans. In the PAT plans, integral dose was significantly reduced by 18% relative to IMPT plans and by 54% relative to VMAT plans. PAT decreased the mean dose to numerous organs-at-risk (OARs), further reducing NTCPs. The ΔNTCP for PAT relative to VMAT passed the NIPP thresholds for 32 out of the 42 patients treated with VMAT, resulting in 180 patients (81%) of the complete cohort qualifying for protons. CONCLUSION: PAT outperforms IMPT and VMAT, leading to a further reduction of NTCP-values and higher ΔNTCP-values, significantly increasing the percentage of OPC patients selected for proton therapy.

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. However, this advantage comes at the expense of longer treatment times. PURPOSE: To exploit the dosimetric advantages of proton arcs, while achieving reasonable delivery times, we propose a partitioning approach where discrete arc plans are split into subplans to be delivered over different fractions in the treatment course. METHODS: For three oropharyngeal cancer patients, four different arc plans have been created and compared to the corresponding clinical IMPT plan. The treatment plans are all planned to be delivered in 35 fractions, but with different delivery approaches over the fractions. The first arc plan (1×30) has 30 directions to be delivered every fraction, while the others are partitioned into subplans with 10 and 6 beam directions, each to be delivered every third (3×10), fifth fraction (5×6), or seventh fraction (7×10). All plans are assessed with respect to delivery time, target robustness over the treatment course, doses to OARs and NTCP for dysphagia and xerostomia. RESULTS: The delivery time (including an additional delay of 30 s between the discrete directions to simulate manual interaction with the treatment control system) is reduced from on average 25.2 min for the 1×30 plan to 9.2 min for the 3×10 and 7×10 plans and 5.7 min for the 5×6 plans. The delivery time for the IMPT plan is 7.9 min. When accounting for the combination of delivery time, target robustness, OAR sparing, and NTCP reduction, the plans with 10 directions in each fraction are the preferred choice. Both the 3×10 and 7×10 plans show improved target robustness compared to the 1×30 plans, while keeping OAR doses and NTCP values at almost as low levels as for the 1×30 plans. For all patients the NTCP values for dysphagia are lower for the partitioned plans with 10 directions compared to the IMPT plans. NTCP reduction for xerostomia compared to IMPT is seen in two of the three patients. The best results are seen for the first patient, where the NTCP reductions for the 7×10 plan are 1.6 p.p. (grade 2 xerostomia) and 1.5 p.p. (grade 2 dysphagia). The corresponding NTCP reductions for the 1×30 plan are 2.7 p.p. (xerostomia, grade 2) and 2.0 p.p. (dysphagia, grade 2). CONCLUSIONS: Discrete proton arcs can be implemented at any proton facility with reasonable treatment times using a partitioning approach. The technique also makes the proton arc treatments more robust to changes in the patient anatomy.

Comparison of the suitability of CBCT- and MR-based synthetic CTs for daily adaptive proton therapy in head and neck patients.

Cone-beam computed tomography (CBCT)- and magnetic resonance (MR)-images allow a daily observation of patient anatomy but are not directly suited for accurate proton dose calculations. This can be overcome by creating synthetic CTs (sCT) using deep convolutional neural networks. In this study, we compared sCTs based on CBCTs and MRs for head and neck (H&N) cancer patients in terms of image quality and proton dose calculation accuracy. A dataset of 27 H&N-patients, treated with proton therapy (PT), containing planning CTs (pCTs), repeat CTs, CBCTs and MRs were used to train two neural networks to convert either CBCTs or MRs into sCTs. Image quality was quantified by calculating mean absolute error (MAE), mean error (ME) and Dice similarity coefficient (DSC) for bones. The dose evaluation consisted of a systematic non-clinical analysis and a clinical recalculation of actually used proton treatment plans. Gamma analysis was performed for non-clinical and clinical treatment plans. For clinical treatment plans also dose to targets and organs at risk (OARs) and normal tissue complication probabilities (NTCP) were compared. CBCT-based sCTs resulted in higher image quality with an average MAE of 40 ± 4 HU and a DSC of 0.95, while for MR-based sCTs a MAE of 65 ± 4 HU and a DSC of 0.89 was observed. Also in clinical proton dose calculations, sCTCBCT achieved higher average gamma pass ratios (2%/2 mm criteria) than sCTMR (96.1% vs. 93.3%). Dose-volume histograms for selected OARs and NTCP-values showed a very small difference between sCTCBCT and sCTMR and a high agreement with the reference pCT. CBCT- and MR-based sCTs have the potential to enable accurate proton dose calculations valuable for daily adaptive PT. Significant image quality differences were observed but did not affect proton dose calculation accuracy in a similar manner. Especially the recalculation of clinical treatment plans showed high agreement with the pCT for both sCTCBCT and sCTMR.

Factors affecting the harmonization of disease-related metabolic brain pattern expression quantification in [18F]FDG-PET (PETMETPAT).

INTRODUCTION: The implementation of spatial-covariance [18F]fluorodeoxyglucose positron emission tomography-based disease-related metabolic brain patterns as biomarkers has been hampered by intercenter imaging differences. Within the scope of the JPND-PETMETPAT working group, we illustrate the impact of these differences on Parkinson's disease-related pattern (PDRP) expression scores. METHODS: Five healthy controls, 5 patients with idiopathic rapid eye movement sleep behavior disorder, and 5 patients with Parkinson's disease were scanned on one positron emission tomography/computed tomography system with multiple image reconstructions. In addition, one Hoffman 3D Brain Phantom was scanned on several positron emission tomography/computed tomography systems using various reconstructions. Effects of image contrast on PDRP scores were also examined. RESULTS: Human and phantom raw PDRP scores were systematically influenced by scanner and reconstruction effects. PDRP scores correlated inversely to image contrast. A Gaussian spatial filter reduced contrast while decreasing intercenter score differences. DISCUSSION: Image contrast should be considered in harmonization efforts. A Gaussian filter may reduce noise and intercenter effects without sacrificing sensitivity. Phantom measurements will be important for correcting PDRP score offsets.