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Background: Chordomas and chondrosarcomas of the skull base are rare, slowly growing malignant bone neoplasms. Despite their radioresistant properties, proton therapy has been successfully used as an adjunct to resection or as a definitive treatment. Herewith, we present our experience with robustly optimized intensity-modulated proton therapy (IMPT) and related toxicities in skull base chordoma and chondrosarcoma patients treated at HollandPTC, Delft, the Netherlands. Methods: Clinical data, treatment plans, and acute toxicities of patients treated between July 2019 and August 2021 were reviewed. CT and 3.0T MRI scans for treatment planning were performed in supine position in a thermoplastic mold. In total, 21 dose optimization and 28 dose evaluation scenarios were simulated. Acute toxicity was scored weekly before and during the treatment according to the CTCAE v4.0. Median follow-up was 35 months (range 12–36 months). Results: Overall, 9 chordoma and 3 chondrosarcoma patients with 1–3 resections prior to IMPT were included; 4 patients had titanium implants. Brainstem core and surface and spinal cord core and surface were used for nominal plan robust optimization in 11, 10, 8, and 7 patients, respectively. Middle ear inflammation, dry mouth, radiation dermatitis, taste disorder, and/or alopecia of grades 1–3 were noted at the end of treatment among 6 patients without similar complaints at inclusion; symptoms disappeared 3 months following the treatment. Conclusion: Robustly optimized IMPT is clinically feasible as a postoperative treatment for skull base chordoma and chondrosarcoma patients. We observed acceptable early toxicities (grade 1–3) that disappeared within the first 3 months after irradiation. [ABSTRACT FROM AUTHOR]

Purpose: The focus of this article is to describe the configuration, testing, and commissioning of a novel gantry-less synchrotron-based proton therapy (PT) facility. Materials and methods: The described PT system delivers protons with a water equivalent range between 4 and 38 cm in 1800 energy layers. The fixed beam delivery permits a maximum field size of 28 × 30 cm2. The patient positioning and imaging system includes a six-degree-of-freedom robotic arm, a convertible patient chair, a vertical 4DCT, and an orthogonal 2D X-ray imaging system. Results: The spot positioning reproducibility was consistent within ±1 mm. The width (σ) of the beam profile at the isocenter was energy dependent and ranged from 2.8 mm to 7.7 mm. Absolute dose reproducibility was measured and deviations were found to be <0.62% for all possible beam scenarios. The built-in dose monitoring system was successfully tested for its ability to generate interlocks under specific conditions (beam spot deviation ≥2 mm, individual spot dose ≥10% or ≥0.25 Gy, spot energy deviation ≥0.5 MeV). The robot positioning exhibited a consistent reproducibility within ±1 mm. All tested scenarios achieved laser-free initial 3D/3D image-guided positioning within ±5 mm. Subsequent 2D/3D positioning showed an accuracy of ±1 mm. A single 2D/3D image registration event corrected positions in all cases. Results of gamma analysis (3%, 3 mm) demonstrated pass rates greater than 95% for head and neck, thorax, abdomen treatment plans. Conclusions: We report on the performance of a novel single-room gantry-less PT system comprised of a compact synchrotron and an adjustable (from nearly horizontal to almost vertical) patient positioning system. The commissioning results show high accuracy and reproducibility of the main proton beam parameters and the patient positioning system. The new PT facility started patient treatments in March 2023, which were the first in Israel and the Middle Eastern region. [ABSTRACT FROM AUTHOR]

Abstract Purpose Respiratory movement, as one of the main challenges in proton therapy for pancreatic cancer patients, could not only lead to harm to normal tissues but also lead to failure of the tumor control, resulting in irreversible consequences. Including respiratory movements into the plan optimization, i.e. 4D robust optimization, may mitigate the interplay effect. However, 4D robust optimization considering images of all breathing phases is time-consuming and less efficient. This work aims to investigate the effect of the breathing phase number on the 4D robust optimization for pancreatic cancer intensity modulated proton therapy (IMPT) by examining plan quality and computational efficiency. Methods A total of 15 pancreatic cancer patients were retrospectively analyzed. In this study, both anterior-fields and posterior-fields plans were created for each patient. For each plan, six four-dimensional (4D) robust treatment planning strategies with different numbers of respiratory phases and one three-dimensional (3D) treatment plan were created. Optimization of the plans were performed on all ten phases (10phase plan), two extreme phases (2phase plan), two extreme phases plus an intermediate state (3phase plan), two extreme phases plus the 3D CT (3Aphase plan), six phases during the exhalation stage (6Exphase plan), six phases during the inhalation stage (6Inphase plan) and 3D Computed Tomography (CT) scan image (3D plan), respectively. 4D dynamic dose (4DDD) was then calculated to access the interplay effect by considering respiratory motion and dynamic beam delivery. Plan quality and dosimetric parameters for the target and organs at risk (OARs) were then analyzed. Results Compared to the 4D plans, 3D plan performed terribly in terms of target coverage and organs at risk. Target dose in anterior-fields plan varied slightly among all six 4D treatment planning strategies. Both the 6Exphase and 6Inphase plans demonstrated performance that was comparable to the 10phase plan in target coverage, outperforming the other five plans for anterior-fields plan. It’s basically the same for the posterior-fields plan. The six strategies showed similar OARs sparing effect for both anterior-fields and posterior-fields plan. Compared with the 10phase plan, the average decline rates of the optimization time of the six plans of 2phase, 3phase, 3Aphase, 6Exphase, 6Inphase, and 3D were 73.26 ± 6.54% vs. 74.48 ± 6.63%, 65.80 ± 7.89% vs. 65.81 ± 9.58%, 54.67 ± 11.52% vs. 65.75 ± 9.58%, 42.14 ± 13.57% vs. 39.63 ± 16.93%, 37.72 ± 11.70% vs. 40.79 ± 13.62% and 75.52 ± 8.21% vs. 80.67 ± 5.62%, respectively (anterior vs. posterior). With the decrease of the number of phases selected for optimization, the decline rates increased, while the other dosimetry parameters generally showed a deterioration trend. Conclusion In this study, a comprehensive evaluation of six 4D robust treatment planning strategies and one 3D treatment planning strategy for pancreatic cancer patients receiving IMPT was performed. The results showed that six 4D robust optimization strategies were comparable in common posterior field therapy. 2phase and 3phase (including 3Aphase) treatment planning strategies could replace the 10phase treatment planning strategy. It should be noted that patients with large motion amplitudes should receive special attention. The dosimetric performance of the 6Exphase and 6Inphase plans closely aligned with that of the 10phase plan in anterior fields. These plans offered a feasible alternative to 10phase treatment planning strategy by reducing optimization time while maintaining dose coverage of the target and protection of OARs. This research provides guidelines to reduce optimization time and improve clinical efficiency for pancreatic cancer IMPT.

Purpose: Respiratory movement, as one of the main challenges in proton therapy for pancreatic cancer patients, could not only lead to harm to normal tissues but also lead to failure of the tumor control, resulting in irreversible consequences. Including respiratory movements into the plan optimization, i.e. 4D robust optimization, may mitigate the interplay effect. However, 4D robust optimization considering images of all breathing phases is time-consuming and less efficient. This work aims to investigate the effect of the breathing phase number on the 4D robust optimization for pancreatic cancer intensity modulated proton therapy (IMPT) by examining plan quality and computational efficiency. Methods: A total of 15 pancreatic cancer patients were retrospectively analyzed. In this study, both anterior-fields and posterior-fields plans were created for each patient. For each plan, six four-dimensional (4D) robust treatment planning strategies with different numbers of respiratory phases and one three-dimensional (3D) treatment plan were created. Optimization of the plans were performed on all ten phases (10phase plan), two extreme phases (2phase plan), two extreme phases plus an intermediate state (3phase plan), two extreme phases plus the 3D CT (3Aphase plan), six phases during the exhalation stage (6Exphase plan), six phases during the inhalation stage (6Inphase plan) and 3D Computed Tomography (CT) scan image (3D plan), respectively. 4D dynamic dose (4DDD) was then calculated to access the interplay effect by considering respiratory motion and dynamic beam delivery. Plan quality and dosimetric parameters for the target and organs at risk (OARs) were then analyzed. Results: Compared to the 4D plans, 3D plan performed terribly in terms of target coverage and organs at risk. Target dose in anterior-fields plan varied slightly among all six 4D treatment planning strategies. Both the 6Exphase and 6Inphase plans demonstrated performance that was comparable to the 10phase plan in target coverage, outperforming the other five plans for anterior-fields plan. It's basically the same for the posterior-fields plan. The six strategies showed similar OARs sparing effect for both anterior-fields and posterior-fields plan. Compared with the 10phase plan, the average decline rates of the optimization time of the six plans of 2phase, 3phase, 3Aphase, 6Exphase, 6Inphase, and 3D were 73.26 ± 6.54% vs. 74.48 ± 6.63%, 65.80 ± 7.89% vs. 65.81 ± 9.58%, 54.67 ± 11.52% vs. 65.75 ± 9.58%, 42.14 ± 13.57% vs. 39.63 ± 16.93%, 37.72 ± 11.70% vs. 40.79 ± 13.62% and 75.52 ± 8.21% vs. 80.67 ± 5.62%, respectively (anterior vs. posterior). With the decrease of the number of phases selected for optimization, the decline rates increased, while the other dosimetry parameters generally showed a deterioration trend. Conclusion: In this study, a comprehensive evaluation of six 4D robust treatment planning strategies and one 3D treatment planning strategy for pancreatic cancer patients receiving IMPT was performed. The results showed that six 4D robust optimization strategies were comparable in common posterior field therapy. 2phase and 3phase (including 3Aphase) treatment planning strategies could replace the 10phase treatment planning strategy. It should be noted that patients with large motion amplitudes should receive special attention. The dosimetric performance of the 6Exphase and 6Inphase plans closely aligned with that of the 10phase plan in anterior fields. These plans offered a feasible alternative to 10phase treatment planning strategy by reducing optimization time while maintaining dose coverage of the target and protection of OARs. This research provides guidelines to reduce optimization time and improve clinical efficiency for pancreatic cancer IMPT. [ABSTRACT FROM AUTHOR]

Background: Intensity Modulated Proton Therapy (IMPT) is a sophisticated radiation treatment allowing for precise dose distributions. However, conventional spot selection strategies in IMPT face challenges, particularly with minimum monitor unit (MU) constraints, affecting planning quality and efficiency. Purpose: This study introduces an innovative Two‐Stage Mixed Integer Linear Programming (MILP) method to optimize spot intensity in IMPT with Lower Bound (LB) constraints. This method seeks to improve treatment planning efficiency and precision, overcoming limitations of existing strategies. Methods: Our approach evaluates prevalent IMPT spot selection strategies, identifying their limitations, especially concerning MU constraints. We integrated LB constraints into a MILP framework, using a novel three‐phase strategy for spot pool selection, to enhance performance over traditional heuristic methods and L1 + L∞ strategies. The method's efficacy was tested in eight study cases, using Dose‐Volume Histograms (DVHs), spot selection efficiency, and computation time analysis for benchmarking against established methods. Results: The proposed method showed superior performance in DVH quality, adhering to LB constraints while maintaining high‐quality treatment plans. It outperformed existing techniques in spot selection, reducing unnecessary spots and balancing precision with efficiency. Cases studies confirmed the method's effectiveness in producing clinically feasible plans with enhanced dose distributions and reduced hotspots, especially in cases with elevated LB constraints. Conclusions: Our Two‐Stage MILP strategy signifies a significant advancement in IMPT treatment planning. By incorporating LB constraints directly into the optimization process, it achieves superior plan quality and deliverability compared to current methods. This approach is particularly advantageous in clinical settings requiring minimum spot number and high MU LB constraints, offering the potential for improved patient outcomes through more precise and efficient radiation therapy plans. [ABSTRACT FROM AUTHOR]

Simple Summary: The overall delivery time of proton arc therapy (PAT) plans on current clinical systems must be evaluated due to high upward energy layer switching times (ELSTs) in order to identify clinically suitable methods of PAT planning and delivery. We present the application of an emulator for modelling the delivery of 'sawtooth' PAT plans on an existing cyclotron-based system. We show that this method of PAT planning consistently requires a longer delivery time than static intensity modulated proton therapy (IMPT) and that delivering PAT using a continuous gantry rotation remains the optimum delivery method on such systems. This analysis shows that the delivery of PAT plans generated using the simplified sawtooth PAT planning approach may be clinically infeasible without further developments to the existing clinical technologies. Purpose: To evaluate and compare the deliverability of 'sawtooth' proton arc therapy (PAT) plans relative to static intensity modulated proton therapy (IMPT) at a cyclotron-based clinical facility. Methods: The delivery of single and dual arc Sawtooth PAT plans for an abdominal CT phantom and multiple clinical cases of brain, head and neck (H&N) and base of skull (BoS) targets was emulated under the step-and-shoot and continuous PAT delivery regimes and compared to that of a corresponding static IMPT plan. Results: Continuous PAT delivery increased the time associated with beam delivery and gantry movement in single/dual PAT plans by 4.86/7.34 min (brain), 7.51/12.40 min (BoS) and 6.59/10.57 min (H&N) on average relative to static IMPT. Step-and-shoot PAT increased this delivery time further by 4.79 min on average as the delivery was limited by gantry motion. Conclusions: The emulator can approximately model clinical sawtooth PAT delivery but requires experimental validation. No clear benefit was observed regarding beam-on time for sawtooth PAT relative to static IMPT. [ABSTRACT FROM AUTHOR]

Simple Summary: Adaptive proton therapy (APT) is an evolving approach to proton beam scanning treatment planning. We performed dosimetric study on two groups of head and neck (H&N) patients to evaluate the influence of plan adaptation on planning target volume (PTV) and organs at risk (OARs) doses, resulting from the changes in patient anatomy observed in control computed tomography (CT). The adapted treatment plans, which incorporated the changes observed in the control CT images, statistically improved mostly PTV coverage compared to initial plan. Study shows that applying adaptive procedures in clinical workflow may increased efficiency by controlling the proper irradiation of the treated area for H&N cancer patients. Applying a proton beam in radiotherapy enables precise irradiation of the tumor volume, but only for continuous assessment of changes in patient anatomy. Proton beam range uncertainties in the treatment process may originate not only from physical beam properties but also from patient-specific factors such as tumor shrinkage, edema formation and sinus filling, which are not incorporated in tumor volume safety margins. In this paper, we evaluated variations in dose distribution in proton therapy resulting from the differences observed in the control tomographic images and the dosimetric influence of applied adaptive treatment. The data from weekly computed tomography (CT) control scans of 21 patients, which serve as the basis for adaptive radiotherapy, were used for this study. Dosimetric analysis of adaptive proton therapy (APT) was performed on patients with head and neck (H&N) area tumors who were divided into two groups: patients with tumors in the sinus/nasal area and patients with tumors in the brain area. For this analysis, the reference treatment plans were forward-calculated using weekly control CT scans. A comparative evaluation of organ at risk (OAR) dose-volume histogram (DVH) parameters, as well as conformity and homogeneity indices, was conducted between the initial and recalculated dose distributions to assess the necessity of the adaptation process in terms of dosimetric parameters. Changes in PTV volume after replanning were observed in seventeen patient cases, showing a discrepancy of over 1 cm 3 in ten cases. In these cases, tumor progression occurred in 30% of patients, while regression was observed in 70%. The statistical analysis indicates that the use of the adaptive planning procedure results in a statistically significant improvement in dose distribution, particularly in the PTV area. The findings led to the conclusion that the adaptive procedure provides significant advantages in terms of dose distribution within the treated volume. However, when considering the entire patient group, APT did not result in a statistically significant dose reduction in OARs (α = 0.05). [ABSTRACT FROM AUTHOR]

PurposeThe focus of this article is to describe the configuration, testing, and commissioning of a novel gantry-less synchrotron-based proton therapy (PT) facility.Materials and methodsThe described PT system delivers protons with a water equivalent range between 4 and 38 cm in 1800 energy layers. The fixed beam delivery permits a maximum field size of 28 × 30 cm2. The patient positioning and imaging system includes a six-degree-of-freedom robotic arm, a convertible patient chair, a vertical 4DCT, and an orthogonal 2D X-ray imaging system.ResultsThe spot positioning reproducibility was consistent within ±1 mm. The width (σ) of the beam profile at the isocenter was energy dependent and ranged from 2.8 mm to 7.7 mm. Absolute dose reproducibility was measured and deviations were found to be

Background: While minimizing plan delivery time is beneficial for proton therapy in terms of motion management, patient comfort, and treatment throughput, it often poses a tradeoff with optimizing plan quality. A key component of plan delivery time is the energy switching time, which is approximately proportional to the number of energy layers, that is, the cardinality. Purpose: This work aims to develop a novel optimization method that can efficiently compute the pareto surface between plan quality and energy layer cardinality, for the planner to navigate through this quality‐and‐efficiency tradeoff and select the appropriate plan of a balanced tradeoff. Methods: A new IMPT method CARD is proposed that (1) explicitly incorporates the minimization of energy layer cardinality as an optimization objective, and (2) automatically generates a set of plans sequentially with a descending order in number of energy layers. The energy layer cardinality is penalized through the l1,0‐norm regularization with an upper bound, and the upper bound is monotonically decreased to compute a series of treatment plans with gradually decreased energy layer cardinality on the quality‐and‐efficiency pareto surface. For any given treatment plan, the plan optimality is enforced using dose‐volume planning objectives and the plan deliverability is imposed through minimum‐monitor‐unit (MMU) constraints, with optimization solution algorithm based on iterative convex relaxation. Results: The new method CARD was validated in comparison with the benchmark plan of all energy layers (P0), and a state‐of‐the‐art method called MMSEL, using prostate, head‐and‐neck (HN), lung, pancreas, liver and brain cases. While labor‐intensive and time‐consuming manual parameter tuning was needed for MMSEL to generate plans of predefined energy layer cardinality, CARD automatically and efficiently computed all plans with sequentially decreasing predefined energy layer cardinality all at once. With the acceptable plan quality (i.e., no more than 110% of total optimization objective value from P0), CARD achieved the reduction of number of energy layers to 52% (from 77 to 40), 48% (from 135 to 65), 59% (from 85 to 50), 67% (from 52 to 35), 80% (from 50 to 40), and 30% (from 66 to 20), for prostate, HN, lung, pancreas, liver, and brain cases, respectively, compared to P0, with overall better plan quality than MMSEL. Moreover, due to the nonconvexity of the MMU constraint, CARD provided the similar or even smaller optimization objective than P0, at the same time with fewer number of energy layers, that is, 55 versus 77, 85 versus 135, 45 versus 52, and 25 versus 66 for prostate, HN, pancreas, and brain cases, respectively. Conclusions: We have developed a novel optimization algorithm CARD that can efficiently and automatically compute a series of treatment plans of any given energy layer sequentially, which allows the planner to navigate through the plan‐quality and energy‐layer‐cardinality tradeoff and select the appropriate plan of a balanced tradeoff. [ABSTRACT FROM AUTHOR]

In pencil-beam-scanning proton therapy, the dose is painted spot-by-spot, layer-by-layer, allowing for significantly more control compared to conventional radiation. This work intends to showcase the impressive ability of intensity-modulated proton therapy (IMPT) to shape complex dose distributions by recreating some of history's most renowned artworks as treatment plans. Five (5) well-recognized paintings were recreated in our clinical treatment planning system using a water phantom as a "canvas" and radiation dose as "paint." For each "painting," colors were assigned to various isodose levels, and the treatment plans were inversely optimized to achieve the desired tones. Using the above methods, we were able to recreate The Starry Night by Vincent Van Gogh, Girl with a Pearl Earring by Johannes Vermeer, and The Scream by Edvard Munch, among others. The results of this work have potential applications in patient education, medical education, and medical physics education by providing a unique and interesting platform for learning. [ABSTRACT FROM AUTHOR]

With complex head and neck diseases that closely approximate crucial organs or have advanced spread and cannot be surgically resected, intensity modulated proton beam radiotherapy is favored due to its superior dose targeting through magnetic manipulation of the proton energy. A radiation mask and an oral positioning device immobilize craniofacial, cervical, and oral structures for accurate and reliable radiation delivery. Widely available prefabricated thermoplastic oral positioning devices are manufactured in standardized forms and materials that unpredictably affect the proton beams' pathways and range. This technique article showcases a workflow that combines analog and digital dental techniques to produce a customized 3D‐printed oral positioning device within 2 appointments. [ABSTRACT FROM AUTHOR]

PurposeProton dose distribution is sensitive to uncertainties in range estimation and patient positioning. Currently, the proton robustness is managed by worst-case scenario optimization methods, which are computationally inefficient. To overcome these challenges, we develop a novel intensity-modulated proton therapy (IMPT) optimization method that integrates dose fidelity with a sensitivity term that describes dose perturbation as the result of range and positioning uncertainties.MethodsIn the integrated optimization framework, the optimization cost function is formulated to include two terms: a dose fidelity term and a robustness term penalizing the inner product of the scanning spot sensitivity and intensity. The sensitivity of an IMPT scanning spot to perturbations is defined as the dose distribution variation induced by range and positioning errors. To evaluate the sensitivity, the spatial gradient of the dose distribution of a specific spot is first calculated. The spot sensitivity is then determined by the total absolute value of the directional gradients of all affected voxels. The fast iterative shrinkage-thresholding algorithm is used to solve the optimization problem. This method was tested on three skull base tumor (SBT) patients and three bilateral head-and-neck (H&N) patients. The proposed sensitivity-regularized method (SenR) was implemented on both clinic target volume (CTV) and planning target volume (PTV). They were compared with conventional PTV-based optimization method (Conv) and CTV-based voxel-wise worst-case scenario optimization approach (WC).ResultsUnder the nominal condition without uncertainties, the three methods achieved similar CTV dose coverage, while the CTV-based SenR approach better spared organs at risks (OARs) compared with the WC approach, with an average reduction of [Dmean, Dmax] of [4.72, 3.38]  GyRBE for the SBT cases and [2.54, 3.33] GyRBE for the H&N cases. The OAR sparing of the PTV-based SenR method was comparable with the WC method. The WC method, and SenR approaches all improved the plan robustness from the conventional PTV-based method. On average, under range uncertainties, the lowest [D95%, V95%, V100%] of CTV were increased from [93.75%, 88.47%, 47.37%] in the Conv method, to [99.28%, 99.51%, 86.64%] in the WC method, [97.71%, 97.85%, 81.65%] in the SenR-CTV method and [98.77%, 99.30%, 85.12%] in the SenR-PTV method, respectively. Under setup uncertainties, the average lowest [D95%, V95%, V100%] of CTV were increased from [95.35%, 94.92%, 65.12%] in the Conv method, to [99.43%, 99.63%, 87.12%] in the WC method, [96.97%, 97.13%, 77.86%] in the SenR-CTV method, and [98.21%, 98.34%, 83.88%] in the SenR-PTV method, respectively. The runtime of the SenR optimization is eight times shorter than that of the voxel-wise worst-case method.ConclusionWe developed a novel computationally efficient robust optimization method for IMPT. The robustness is calculated as the spot sensitivity to both range and shift perturbations. The dose fidelity term is then regularized by the sensitivity term for the flexibility and trade-off between the dosimetry and the robustness. In the stress test, SenR is more resilient to unexpected uncertainties. These advantages in combination with its fast computation time make it a viable candidate for clinical IMPT planning.

Aim: We propose a novel metric called ψ -- score to rank the Intensity Modulated Proton Therapy (IMPT) beams in the order of their optimality and robustness. The beams ranked based on this metric were accordingly chosen for IMPT optimization. The objective of this work is to study the effectiveness of the proposed method in various clinical cases. Methods and Materials: We have used Pinnacle TPS (Philips Medical System V 16.2) for performing the optimization. To validate our approach, we have applied it in four clinical cases: Lung, Pancreas, Prostate+Node and Prostate. Basically, for all clinical cases, four set of plans were created using Multi field optimization (MFO) and Robust Optimization (RO) with same clinical objectives, namely (1) Conventional angle plan without Robust Optimization (CA Plan), (2) Suitable angle Plan without Robust Optimization (SA Plan), (3) Conventional angle plan with Robust Optimization (CA-RO Plan), (4) Suitable angle Plan with Robust Optimization (SA-RO Plan). Initial plan was generated with 20 equiangular beams starting from the gantry angle of 0°. In the corresponding SA Plan and SA-RO Plan, the beam angles were obtained using the guidance provided by ψ -- score. Results: All CA plans were compared against the SA plans in terms of Dose distribution, Dose volume histogram (DVH) and percentage of dose difference. The results obtained from the clinical cases indicate that the plan quality is considerably improved without significantly compromising the robustness when the beam angles are optimized using the proposed method. It takes approximately 10--15 min to find the suitable beam angles without Robust Optimization (RO), while it takes approximately 20-30 min to find the suitable beam angles with RO. However, the inclusion of RO in BAO did not result in a change in the final beam angles for anatomies other than lung. Conclusion: The results obtained in different anatomic sites demonstrate the usefulness of our approach in improving the plan quality by determining optimal beam angles in IMPT. [ABSTRACT FROM AUTHOR]

Background: Intensity Modulated Proton Therapy (IMPT) in head and neck cancer (HNC) is susceptible to anatomical changes and patient set-up inaccuracies during the radiotherapy course, which can cause discrepancies between planned and delivered dose. The discrepancies can be counteracted by adaptive replanning strategies. This article reviews the observed dosimetric impact of adaptive proton therapy (APT) and the timing to perform a plan adaptation in IMPT in HNC. Methods: A literature search of articles published in PubMed/MEDLINE, EMBASE and Web of Science from January 2010 to March 2022 was performed. Among a total of 59 records assessed for possible eligibility, ten articles were included in this review. Results: Included studies reported on target coverage deterioration in IMPT plans during the RT course, which was recovered with the application of an APT approach. All APT plans showed an average improved target coverage for the high- and low-dose targets as compared to the accumulated dose on the planned plans. Dose improvements up to 2.5 Gy (3.5 %) and up to 4.0 Gy (7.1 %) in the D98 of the high- and low dose targets were observed with APT. Doses to the organs at risk (OARs) remained equal or decreased slightly after APT was applied. In the included studies, APT was largely performed once, which resulted in the largest target coverage improvement, but eventual additional APT improved the target coverage further. There is no data showing what is the most appropriate timing for APT. Conclusion: APT during IMPT for HNC patients improves target coverage. The largest improvement in target coverage was found with a single adaptive intervention, and an eventual second or more frequent APT application improved the target coverage further. Doses to the OARs remained equal or decreased slightly after applying APT. The most optimal timing for APT is yet to be determined.

• The plan library (PL) for H&N IMPT was compared to conventional treatments. • The PL resulted in overall reduced NTCPs at limited cost in target coverage. • If NTCP was worse, adherence to target constraints could sometimes be improved. • The PL is a relatively simple online adaptive strategy to implement in clinics. In intensity modulated proton therapy (IMPT), the impact of setup errors and anatomical changes is commonly mitigated by robust optimization with population-based setup robustness (SR) settings and offline replanning. In this study we propose and evaluate an alternative approach based on daily plan selection from patient-specific pre-treatment established plan libraries (PLs). Clinical implementation of the PL strategy would be rather straightforward compared to daily online re-planning. For 15 head-and-neck cancer patients, the planning CT was used to generate a PL with 5 plans, robustly optimized for increasing SR: 0, 1, 2, 3, 5 mm, and 3% range robustness. Repeat CTs (rCTs) and realistic setup and range uncertainty distributions were used for simulation of treatment courses for the PL approach, treatments with fixed SR (fSR 3) and a trigger-based offline adaptive schedule for 3 mm SR (fSR 3 OfA). Daily plan selection in the PL approach was based only on recomputed dose to the CTV on the rCT. Compared to using fSR 3 and fSR 3 OfA, the risk of xerostomia grade ≥ II & III and dysphagia ≥ grade III were significantly reduced with the PL. For 6/15 patients the risk of xerostomia and/or dysphagia ≥ grade II could be reduced by > 2% by using PL. For the other patients, adherence to target coverage constraints was often improved. fSR 3 OfA resulted in significantly improved coverage compared to PL for selected patients. The proposed PL approach resulted in overall reduced NTCPs compared to fSR 3 and fSR 3 OfA at limited cost in target coverage. [ABSTRACT FROM AUTHOR]

Objective. This study aims to determine a margin and robustness setting for treating locally advanced cervical cancer (LACC) with a library-of-plans (LoP) based online-adaptive intensity-modulated proton therapy (IMPT). Approach. We analyzed 13 LACC patients with delineated planning and weekly repeat CT scans (reCTs). For each patient, 120 IMPT treatments of 25 fractions were simulated with a LoPs approach. Six different robustness settings (2-7 mm set-up robustness (SR) plus 3% range robustness (RR)) were used to create those 120 IMPT plans. Each fraction was simulated with a weekly reCT, combined with the sampling of inter- and intrafraction treatment uncertainties. The fraction doses were accumulated to obtain a treatment dose to the target volumes, distinguishing between the low-risk clinical target volume (CTV-T-LR) and the elective CTV (CTV-E). If one of the two targets obtained an adequate coverage for more than 90% of the treatments, different anisotropic margins were sampled on top of the robustness setting to the other target to obtain the Pareto-optimal margin in terms of adequate coverage versus increase in target volume. Main results. The percentage of treatments that reach the dose criterion V 42.75Gy > 95% for the CTV-T-LR was 22.3%, 28.5%, 51.2%, 73.1%, 85.3%, and 90.0% for 2, 3, 4, 5, 6, and 7 mm SR plus 3% RR and for the CTV-E, this percentage was 60.4%, 73.8%, 86.5%, 92.3%, 96.9%, and 98.5%. The Pareto-optimal margin combined with a 5 mm/3% robustness setting for the CTV-T-LR with an adequate coverage for >90% of the treatments was given by {0, 1, 0, 3, 3, 0} mm in the left, right, anterior, posterior, cranial, caudal direction. Significance. Our study evaluated combinations of robustness and anisotropic margin settings for IMPT for LACC. With 5 mm SR and 3% RR for CTV-E and CTV-T-LR plus a margin to the CTV-T-LR of {0, 1, 0, 3, 3, 0} mm in left, right, anterior, posterior, cranial, and caudal ensured an adequate coverage for >90% of the simulated IMPT treatments., (Creative Commons Attribution license.)

Aim: The aim of the study was to investigate the hybrid robust optimization planning approach in intensity-modulated proton therapy (IMPT) of craniospinal irradiation (CSI).Subjects and Methods: Five IMPT-based adult CSI plans in supine position were created using Raystation treatment planning system (TPS) modelled for Proteus plus proton therapy system. A hybrid planning strategy was implemented, where clinical target volume was robustly optimized (RB) for set up uncertainties and planning target volume was optimized for target coverage using minimax algorithm in the TPS. Beam angle selection, optimization, and dose calculation approach were carefully performed to ensure optimum organ at risk (OAR) sparing, even with potential setup and range errors. The complementary dose gradients in junctions were generated using spot assignment and RB technique. Dosimetric outcomes in both nominal plan and the 16 error scenarios (±3 mm setup and 3.5% range) were analyzed using standard dose volume histogram.Results: This planning approach resulted in a homogeneous dose distribution in the target volume of CSI, including the junction regions, by explicitly reducing number of robust optimization scenarios. The proposed technique was also able to achieve excellent coverage to cribriform plate with lower lens doses and minimal dose to other OARs. Target and OAR doses in the nominal plans as well as in the worst case scenarios with setup and range errors were able to meet the predefined clinical goal.Conclusions: This proposed planning technique is efficient, robust against the uncertainties. It could be adopted in other proton therapy centers. [ABSTRACT FROM AUTHOR]

Proton therapy for cervical esophageal cancer has many issues to be considered, such as the physiological curvature of the spine and the large range change from the neck to the trunk. We clarified the dosimetric characteristics of intensity modulated proton therapy (IMPT) for cervical esophageal cancer by comparing with volumetric modulated arc therapy (VMAT). Ten patients with cervical esophageal cancer were retrospectively planned for VMAT, 2-field IMPT (2F-IMPT), and 3-field IMPT (3F-IMPT). All plans were optimized to reach clinically acceptable levels. For planning target volume (PTV) coverage, 95% of the PTV should be covered by 95% of the prescription dose, unless the spinal cord limit is violated. The organs at risk included the lung, spinal cord, larynx, skin, and whole body. The prescription dose was 60 Gy relative biological effectiveness (RBE) in 30 fractions to the PTV. We compared the results according to dose–volume metrics. Significant dose reductions were achieved at lung doses, especially at low dose volumes of 20 Gy RBE or less in IMPT plans compared with VMAT plans (p < 0.05). Although the spinal cord PRV was below the tolerance level, the results were also significantly higher in VMAT plans than in IMPT plans (p < 0.001). Spinal cord PRV D mean was significantly higher in 3F-IMPT than in 2F-IMPT (p < 0.001). In addition, it was confirmed that the integral whole body dose can be dramatically reduced in IMPT plans compared with VMAT plans. Both of 2F-IMPT and 3F-IMPT could effectively reduce spinal cord dose, as well as low integral whole body dose to a certain extent, while maintaining similar target coverage compared to VMAT. IMPT could be a promising treatment technique for patients with cervical esophageal cancer. [ABSTRACT FROM AUTHOR]

Purpose: The effects of FLASH-level dose rates delivered at the spread-out Bragg peak (SOBP) on normal tissue damage in mice were investigated. Materials and Methods: Fifty nontumor-bearing mice received abdominal irradiation, 30 at FLASH dose rates (100 Gy/s) and 20 at conventional dose rates (0.1 Gy/s). Total dose values ranged from 10 to 19 Gy, delivered in a single spot by a synchrocyclotron proton therapy system. Centered on the abdomen, the collimated field delivered was an 11-mm diameter circle with a water-equivalent depth of 2.4 cm from entrance to distal 80% dose. A ridge filter was used to provide dose uniformity over the full 2.4-cm range. The spatial distribution was identical for both the FLASH and conventional deliveries. Results: Overall survival and individual mouse weights were tracked for 21 days after the exposure date, and LD50 values were compared for the FLASH and conventional dose rate groups. Mice exposed to FLASH dose rates had a higher LD50 value as compared with mice exposed to conventional dose rates, with a dose-dependent improvement in survivability of 10% to 20%. The FLASH cohort also showed greater or equal percent population survival for each day of the study. Conclusion: These results are preliminary confirmation of the potential for the combination of the advantages of the Bragg peak with the normal tissue sparing benefits of FLASH treatments. This experiment also confirms that pulsed synchrocyclotrons can be used for the purpose of FLASH research and treatment.

BackgroundIntensity-modulated proton therapy (IMPT), non-coplanar 4π intensity-modulated radiation therapy (IMRT), and volumetric-modulated arc therapy (VMAT) represent the most advanced treatment methods based on heavy ion and X-rays, respectively. Here we compare their performance for prostate cancer treatment.MethodsTen prostate patients were planned using IMPT with robustness optimization, VMAT, and 4π to an initial dose of 54 Gy to a clinical target volume (CTV) that encompassed the prostate and seminal vesicles, then a boost prescription dose of 25.2 Gy to the prostate for a total dose of 79.2 Gy. The IMPT plans utilized two coplanar, oblique scanning beams 10° posterior of the lateral beam positions. Range uncertainties were taken into consideration in the IMPT plans. VMAT plans used two full, coplanar arcs to ensure sufficient PTV coverage. 4π plans were created by inversely selecting and optimizing 30 beams from 1162 candidate non-coplanar beams using a greedy column generation algorithm. CTV doses, bladder and rectum dose volumes (V40, V45, V60, V65, V70, V75, and V80), R100, R50, R10, and CTV homogeneity index (D95/D5) were evaluated.ResultsCompared to IMPT, 4π resulted in lower anterior rectal wall mean dose as well as lower rectum V40, V45, V60, V65, V70, and V75. Due to the opposing beam arrangement, IMPT resulted in significantly (p

• IMPT in esophageal cancer is robust for anatomical variations and breathing motion. • Adaptation is most effective in the first week of treatment. • Diaphragm baseline shift and changes in water equivalent depth of the ITV cause underdosage. In this study, we assessed the robustness of intensity modulated proton therapy (IMPT) in esophageal cancer for anatomical variations during treatment. The first sixty esophageal cancer patients, treated clinically with chemoradiotherapy were included. The treatment planning strategy was based on an internal target volume (ITV) approach, where the ITV was created from the clinical target volumes (CTVs) delineated on all phases of a 4DCT. For optimization, a 3 mm isotropic margin was added to the ITV, combined with robust optimization using 5 mm setup and 3 % range uncertainty. Each patient received weekly repeat CTs (reCTs). Robust plan re-evaluation on all reCTs, and a robust dose summation was performed. To assess the factors influencing ITV coverage, a multivariate linear regression analysis was performed. Additionally, clinical adaptations were evaluated. The target coverage was adequate (ITV V94%>98 % on the robust voxel-wise minimum dose) on most reCTs (91 %), and on the summed dose in 92 % of patients. Significant predictors for ITV coverage in the multivariate analysis were diaphragm baseline shift and water equivalent depth (WED) of the ITV in the beam direction. Underdosage of the ITV mainly occurred in week 1 and 4, leading to treatment adaptation of eight patients, all on the first reCT. Our IMPT treatment of esophageal cancer is robust for anatomical variations. Adaptation appears to be most effective in the first week of treatment. Diaphragm baseline shifts and WED are predictive factors for ITV underdosage, and should be incorporated in an adaptation protocol. [ABSTRACT FROM AUTHOR]

Simple Summary: Radiation treatment plays a pivotal a role in the management of pancreatic cancer, mainly in the neoadjuvant setting for borderline resectable tumors and in the definitive setting for unresectable localized disease. Most of the studies on pancreatic cancer use photon-based radiation therapy modalities. However, there is a growing interest in the application of protons therapy for gastrointestinal cancers. This review summarizes the literature on the use of proton therapy in the management of pancreatic cancer. Radiation therapy plays a central role in the treatment of pancreatic cancer. While generally shown to be feasible, proton irradiation, particularly when an ablative dose is planned, remains a challenge, especially due to tumor motion and the proximity to organs at risk, like the stomach, duodenum, and bowel. Clinically, standard doses of proton radiation treatment have not been shown to be statistically different from photon radiation treatment in terms of oncologic outcomes and toxicity rates as per non-randomized comparative studies. Fractionation schedules and concurrent chemotherapy combinations are yet to be optimized for proton therapy and are the subject of ongoing trials. [ABSTRACT FROM AUTHOR]

• Proton therapy for inflammatory breast cancer achieves excellent target coverage. • Proton therapy results in low exposure to organs at risk. • Excellent locoregional outcomes with no locoregional recurrences at 2 years. • Toxicity profile is favorable; modest increase in rib fracture. Inflammatory breast cancer (IBC) poses a radiotherapeutic challenge due to dermal lymphatic involvement, which often necessitates larger target volumes and chest wall boosts, making advanced planning techniques attractive to reduce exposure to nearby organs. We report our experience with intensity modulated proton therapy (IMPT) for the treatment of IBC. Between 2016 and 2020, all IBC patients treated with adjuvant IMPT at our institution were identified. Overall survival (OS) and distant metastasis-free survival (DMFS) were estimated using the Kaplan-Meier method. Adverse events (AEs) were assessed using CTCAE version 5.0. Nineteen patients were identified with median 24-month follow-up. CTVs included skin, chest wall, and regional lymph nodes. Median dose was 50 Gy in 25 fractions, with fifteen receiving chest wall boost (median 56.25 Gy in 25 fractions). During treatment, plan re-optimization was required in 9 (47%). Acute grade 3 dermatitis occurred in 2 (11%). Rib facture occurred in 4 (21%). One patient with pre-existing surgical seroma experienced a grade 3 fistula. Mean heart, left anterior descending artery, and right coronary artery doses were 0.7 Gy, 2.3 Gy, and 0.1 Gy, respectively. Mean ipsilateral lung V20Gy was 14.9%. At 2 years, there were no locoregional recurrences, and OS and DMFS were 89% and 82%, respectively. IMPT for IBC is well-tolerated with excellent dosimetry, low rates of AEs, and favorable early locoregional control outcomes. Follow-up for long-term outcomes is ongoing. Our findings suggest that IMPT is feasible and an attractive modality worthy of further investigation in patients with IBC. [ABSTRACT FROM AUTHOR]

Purpose: To explore the role of using Pencil Beam Scanning (PBS) proton beam therapy in single lesion brain stereotactic radiosurgery (SRS), we developed and validated a dosimetric in silico model to assist in the selection of an optimal treatment approach among the conventional Volumetric Modulated Arc Therapy (VMAT), Intensity Modulated Proton Therapy (IMPT) and Spot-scanning Proton Arc (SPArc). Material and Methods: A patient's head CT data set was used as an in silico model. A series of targets (volume range from 0.3 cc to 33.03 cc) were inserted in the deep central and peripheral region, simulating targets with different sizes and locations. Three planning groups: IMPT, VMAT, and SPArc were created for dosimetric comparison purposes and a decision tree was built based on this in silico model. Nine patients with single brain metastases were retrospectively selected for validation. Multiple dosimetric metrics were analyzed to assess the plan quality, such as dose Conformity Index (CI) (ratio of the target volume to 100% prescription isodose volume); R50 (ratio of 50% prescription isodose volume to the target volume); V12Gy (volume of brain tissue minus GTV receiving 12 Gy), and mean dose of the normal brain. Normal tissue complication probability (NTCP) of brain radionecrosis (RN) was calculated using the Lyman-Kutcher-Burman (LKB) model and total treatment delivery time was calculated. Six physicians from different institutions participated in the blind survey to evaluate the plan quality and rank their choices. Results: The study showed that SPArc has a dosimetric advantage in the V12Gy and R50 with target volumes > 9.00 cc compared to VMAT and IMPT. A significant clinical benefit can be found in deep centrally located lesions larger than 20.00 cc using SPArc because of the superior dose conformity and mean dose reduction in healthy brain tissue. Nine retrospective clinical cases and the blind survey showed good agreement with the in silico dosimetric model and decision tree. Additionally, SPArc significantly reduced the treatment delivery time compared to VMAT (SPArc 184.46 ± 59.51s vs. VMAT: 1574.78 ± 213.65s). Conclusion: The study demonstrated the feasibility of using Proton beam therapy for single brain metastasis patients utilizing the SPArc technique. At the current stage of technological development, VMAT remains the current standard modality of choice for single lesion brain SRS. The in silico dosimetric model and decision tree presented here could be used as a practical clinical decision tool to assist the selection of the optimal treatment modality among VMAT, IMPT, and SPArc in centers that have both photon and proton capabilities. [ABSTRACT FROM AUTHOR]

PurposeTo explore the role of using Pencil Beam Scanning (PBS) proton beam therapy in single lesion brain stereotactic radiosurgery (SRS), we developed and validated a dosimetric in silico model to assist in the selection of an optimal treatment approach among the conventional Volumetric Modulated Arc Therapy (VMAT), Intensity Modulated Proton Therapy (IMPT) and Spot-scanning Proton Arc (SPArc).Material and MethodsA patient’s head CT data set was used as an in silico model. A series of targets (volume range from 0.3 cc to 33.03 cc) were inserted in the deep central and peripheral region, simulating targets with different sizes and locations. Three planning groups: IMPT, VMAT, and SPArc were created for dosimetric comparison purposes and a decision tree was built based on this in silico model. Nine patients with single brain metastases were retrospectively selected for validation. Multiple dosimetric metrics were analyzed to assess the plan quality, such as dose Conformity Index (CI) (ratio of the target volume to 100% prescription isodose volume); R50 (ratio of 50% prescription isodose volume to the target volume); V12Gy (volume of brain tissue minus GTV receiving 12 Gy), and mean dose of the normal brain. Normal tissue complication probability (NTCP) of brain radionecrosis (RN) was calculated using the Lyman-Kutcher-Burman (LKB) model and total treatment delivery time was calculated. Six physicians from different institutions participated in the blind survey to evaluate the plan quality and rank their choices.ResultsThe study showed that SPArc has a dosimetric advantage in the V12Gy and R50 with target volumes > 9.00 cc compared to VMAT and IMPT. A significant clinical benefit can be found in deep centrally located lesions larger than 20.00 cc using SPArc because of the superior dose conformity and mean dose reduction in healthy brain tissue. Nine retrospective clinical cases and the blind survey showed good agreement with the in silico dosimetric model and decision tree. Additionally, SPArc significantly reduced the treatment delivery time compared to VMAT (SPArc 184.46 ± 59.51s vs. VMAT: 1574.78 ± 213.65s).ConclusionThe study demonstrated the feasibility of using Proton beam therapy for single brain metastasis patients utilizing the SPArc technique. At the current stage of technological development, VMAT remains the current standard modality of choice for single lesion brain SRS. The in silico dosimetric model and decision tree presented here could be used as a practical clinical decision tool to assist the selection of the optimal treatment modality among VMAT, IMPT, and SPArc in centers that have both photon and proton capabilities.

Abstract Background Both plan quality and robustness were investigated through comparing some dosimetric metrics between intensity modulated proton therapy (IMPT) and helical tomotherapy based intensity modulated radiotherapy (IMRT) for cervical cancer. Methods Both a spot-scanning robust (SRO) IMPT plan and a helical tomotherapy robust (TRO) IMRT plan were generated for each of 18 patients. In order to evaluate the quality of nominal plans without dose perturbations, planning scores (PS) on clinical target volume (CTV) and five organs at risk (OARs) based on clinical experience, and normal tissue complication probabilities (NTCP) of rectum and sigmoid were calculated based on Lyman-Kutcher-Burman (LKB) model. Dose volume histogram bands width (DVHBW) were calculated in 28 perturbed scenarios to evaluate plan robustness. Results Compared with TRO, the average scores of SRO nominal plans were higher in target metrics [V 46.8Gy , V 50Gy , Conformity and Homogeneity](16.5 vs. 15.1), and in OARs metrics (60.9 vs. 53.3), including bladder [V 35 ,V 45 , D mean ,D 2cc ], rectum [V 40 ,V 45 ,D 2cc ,D max ], bowel [V 35 ,V 40 ,V 45 , D max ], sigmoid [V 40 ,D max ] and femoral heads [V 30 ,D max ]. Meanwhile, NTCP calculation showed that the toxicities of rectum and sigmoid in SRO were lower than those in TRO (rectum: 2.8% vs. 4.8%, p

Purpose/objective: To perform a dosimetric and a normal tissue complication probability (NTCP) comparison between intensity modulated proton therapy and photon volumetric modulated arc therapy in a cohort of patients with parotid gland cancers in a post-operative or radical setting., Materials and Methods: From May 2011 to September 2021, 37 parotid gland cancers patients treated at two institutions were eligible. Inclusion criteria were as follows: patients aged ⩾ 18 years, diagnosis of parotid gland cancers candidate for postoperative radiotherapy or definitive radiotherapy, presence of written informed consent for the use of anonymous data for research purposes. Organs at risk (OARs) were retrospectively contoured. Target coverage goal was defined as D95 > 98%. Six NTCP models were selected. NTCP profiles were calculated for each patient using an internally-developed Python script in RayStation TPS. Average differences in NTCP between photon and proton plans were tested for significance with a two-sided Wilcoxon signed-rank test., Results: Seventy-four plans were generated. A lower Dmean to the majority of organs at risk (inner ear, cochlea, oral cavity, pharyngeal constrictor muscles, contralateral parotid and submandibular gland) was obtained with intensity modulated proton therapy vs volumetric modulated arc therapy with statistical significance (p < .05). Ten (27%) patients had a difference in NTCP (photon vs proton plans) greater than 10% for hearing loss and tinnitus: among them, seven qualified for both endpoints, two patients for hearing loss only, and one for tinnitus., Conclusions: In the current study, nearly one-third of patients resulted eligible for proton therapy and they were the most likely to benefit in terms of prevention of hearing loss and tinnitus., Competing Interests: Declaration of conflicting interestThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: The Division of Radiation Oncology of IEO received Institutional grants from Accuray InC. and Ion Beam Applications (IBA). BAJF received speakers’ fees from Roche, Bayer, Janssen, Carl Zeiss, Ipsen, Accuray, Astellas, Elekta, IBA and Astra Zeneca (all outside the current project). The remaining authors declare no conflicts of interest.

• Robust planning is feasible in proton beam therapy of chordoma and chondrosarcoma patients. • Despite robust planning, plan adaptations are still required in case of anatomical changes. • Monitoring of anatomical changes is warranted. Due to its specific physical characteristics, proton irradiation is especially suited for irradiation of chordomas and chondrosarcoma in the axial skeleton. Robust plan optimization renders the proton beam therapy more predictable upon individual setup errors. Reported experience with the planning and delivery of robustly optimized plans in chordoma and chondrosarcoma of the mobile spine and sacrum, is limited. In this study, we report on the clinical use of robustly optimized, intensity modulated proton beam therapy in these patients. We retrospectively reviewed patient, treatment and acute toxicity data of all patients with chordoma and chondrosarcoma of the mobile spine and sacrum, treated between 1 April 2019 and 1 April 2020 at our institute. Anatomy changes during treatment were evaluated by weekly cone-beam CTs (CBCT), supplemented by scheduled control-CTs or ad-hoc control-CTs. Acute toxicity was scored weekly during treatment and at 3 months after therapy according to CTCAE 4.0. 17 chordoma and 3 chondrosarcoma patients were included. Coverage of the high dose clinical target volume was 99.8% (range 56.1–100%) in the nominal and 80.9% (range 14.3–99.6%) in the voxel-wise minimum dose distribution. Treatment plan adaptation was needed in 5 out of 22 (22.7%) plans. Reasons for plan adaptation were either reduced tumor coverage or increased dose to the OAR. Robustly optimized intensity modulated proton beam therapy for chordoma and chondrosarcoma of the mobile spine is feasible. Plan adaptations due to anatomical changes were required in approximately 23 percent of treatment courses. [ABSTRACT FROM AUTHOR]

• Filtered back projection (FBP) and DirectDensity (DD) algorithms were compared. • The range variations were often less than the calculation grid in case of DD. • DD was more robust with respect to variations in the CT imaging conditions than FBP. • DD is effective in a robust workflow and reduces uncertainties in range calculations. Accurate calculation of the proton beam range inside a patient is an important topic in proton therapy. In recent times, a computed tomography (CT) image reconstruction algorithm was developed for treatment planning to reduce the impact of the variation of the CT number with changes in imaging conditions. In this study, we investigated the usefulness of this new reconstruction algorithm (DirectDensity™: DD) in proton therapy based on its comparison with filtered back projection (FBP). We evaluated the effects of variations in the X-ray tube potential and target size on the FBP- and DD-image values and investigated the usefulness of the DD algorithm based on the range variations and dosimetric quantity variations. For X-ray tube potential variations, the range variation in the case of FBP was up to 12.5 mm (20.8%), whereas that of DD was up to 3.3 mm (5.6%). Meanwhile, for target size variations, the range variation in the case of FBP was up to 2.2 mm (2.5%), whereas that of DD was up to 0.9 mm (1.4%). Moreover, the variations observed in the case of DD were smaller than those of FBP for all dosimetric quantities. The dose distributions obtained using DD were more robust against variations in the CT imaging conditions (X-ray tube potential and target size) than those obtained using FBP, and the range variations were often less than the dose calculation grid (2 mm). Therefore, the DD algorithm is effective in a robust workflow and reduces uncertainty in range calculations. [ABSTRACT FROM AUTHOR]

Purpose: Intensity modulated proton therapy (IMPT) could yield high linear energy transfer (LET) in critical structures and increased biological effect. For head and neck cancers at the skull base this could potentially result in radiation-associated brain image change (RAIC). The purpose of the current study was to investigate voxel-wise dose and LET correlations with RAIC after IMPT.Methods and Materials: For 15 patients with RAIC after IMPT, contrast enhancement observed on T1-weighted magnetic resonance imaging was contoured and coregistered to the planning computed tomography. Monte Carlo calculated dose and dose-averaged LET (LETd) distributions were extracted at voxel level and associations with RAIC were modelled using uni- and multivariate mixed effect logistic regression. Model performance was evaluated using the area under the receiver operating characteristic curve and precision-recall curve.Results: An overall statistically significant RAIC association with dose and LETd was found in both the uni- and multivariate analysis. Patient heterogeneity was considerable, with standard deviation of the random effects of 1.81 (1.30-2.72) for dose and 2.68 (1.93-4.93) for LETd, respectively. Area under the receiver operating characteristic curve was 0.93 and 0.95 for the univariate dose-response model and multivariate model, respectively. Analysis of the LETd effect demonstrated increased risk of RAIC with increasing LETd for the majority of patients. Estimated probability of RAIC with LETd = 1 keV/µm was 4% (95% confidence interval, 0%, 0.44%) and 29% (95% confidence interval, 0.01%, 0.92%) for 60 and 70 Gy, respectively. The TD15 were estimated to be 63.6 and 50.1 Gy with LETd equal to 2 and 5 keV/µm, respectively.Conclusions: Our results suggest that the LETd effect could be of clinical significance for some patients; LETd assessment in clinical treatment plans should therefore be taken into consideration. [ABSTRACT FROM AUTHOR]

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 1.05 g/cm3 during plan optimization. The override was applied to the excursion of the diaphragm between exhale and inhale. Initial robustness evaluation was performed for plan acceptance (setup errors of 8 mm, range errors of ±3%), and subsequently, on all weekly repeated 4DCTs (setup errors of 2 mm, range errors of ±3%). Target coverage and hotspots were analyzed on the resulting voxel‐wise minimum (Vwmin) and voxel‐wise maximum (Vwmax) dose distributions. Results: The nominal dose distributions were similar for both WDO and NDO plans. However, visual inspection of the Vwmax of the WDO plans showed hotspots behind the right diaphragm override region. For one patient, target coverage and hotspots improved by applying the diaphragm override. We found no differences in target coverage in the weekly evaluations between the two approaches. Conclusion: The diaphragm override approach did not result in a clinical benefit in terms of planning and interfractional robustness. Therefore, we do not see added value in employing this approach as a default option during robust optimization for IMPT planning in esophageal cancer. [ABSTRACT FROM AUTHOR]

Proton therapy for breast cancer treatment reduces cardiac radiation exposure. Left-sided breast cancer patients with indication for internal mammary chain (IMC) irradiation are most at risk of radiation-induced cardiotoxicity. This study aims to evaluate in this situation the potential dosimetric benefit of intensity modulated proton therapy (IMPT) over volumetric modulated arc therapy (VMAT) at the cardiac substructure level. Cardiac substructures were retrospectively delineated according to ESTRO guidelines on the simulation CT scans of fourteen left-sided breast cancer patients having undergone conserving surgery and adjuvant locoregional free-breathing (FB-) or deep inspiration breath-hold (DIBH-) VMAT with internal mammary chain irradiation. IMPT treatment was re-planned on the simulation CT scans. Mean doses to cardiac substructures were retrieved and compared between VMAT treatment plans and IMPT simulation plans. Pearson correlation coefficients were calculated between mean doses delivered to cardiac substructures using these two techniques. Mean doses to all cardiac substructures were significantly lower with IMPT than with VMAT. Regardless of the irradiation technique, the most exposed cardiac substructure was the mid segment of the left anterior descending coronary artery (LADCA). Pearson correlation coefficients between mean doses to cardiac substructures were usually weak and statistically non-significant for IMPT; mean heart dose (MHD) only correlated with mean doses delivered to the right ventricle, to the mid segment of the right coronary artery (RCA) and, to a lesser extent, to the LADCA. The dosimetric benefit of IMPT over conformal photon therapy was consistently observed for all cardiac substructures. MHD may not be a reliable dosimetric parameter for precise cardiac exposure evaluation when planning IMPT. [ABSTRACT FROM AUTHOR]

Abstract Background To investigate the role of intensity modulated proton therapy (IMPT) compared to volumetric modulated arc therapy (VMAT) for advanced supradiaphragmatic Hodgkin’s lymphoma (HL) in young female patients by assessing dosimetric features and modelling the risk of treatment related complications and radiation-induced secondary malignancies. Methods A group of 20 cases (planned according to the involved-site approach) were retrospectively investigated in a comparative planning study. Intensity modulated proton plans (IMPT) were compared to VMAT RapidArc plans (RA). Estimates of toxicity were derived from normal tissue complication probability (NTCP) calculations with either the Lyman or the Poisson models for a number of endpoints. Estimates of the risk of secondary cancer induction were determined for lungs, breasts, esophagus and thyroid. A simple model-based selection strategy was considered as a feasibility proof for the individualized selection of patients suitable for proton therapy. Results IMPT and VMAT plans resulted equivalent in terms of target dose distributions, both were capable to ensure high coverage and homogeneity. In terms of conformality, IMPT resulted ~ 10% better than RA plans. Concerning organs at risk, IMPT data presented a systematic improvement (highly significant) over RA for all organs, particularly in the dose range up to 20Gy. This lead to a composite average reduction of NTCP of 2.90 ± 2.24 and a reduction of 0.26 ± 0.22 in the relative risk of cardiac failures. The excess absolute risk per 10,000 patients-years of secondary cancer induction was reduced, with IMPT, of 9.1 ± 3.2, 7.2 ± 3.7 for breast and lung compared to RA. The gain in EAR for thyroid and esophagus was lower than 1. Depending on the arbitrary thresholds applied, the selection rate for proton treatment would have ranged from 5 to 75%. Conclusion In relation to young female patients with advanced supradiaphragmatic HL, IMPT can in general offer improved dose-volume sparing of organs at risk leading to an anticipated lower risk of early or late treatment related toxicities. This would reflect also in significantly lower risk of secondary malignancies induction compared to advanced photon based techniques. Depending on the selection thresholds and with all the limits of a non-validated and very basic model, it can be anticipated that a significant fraction of patients might be suitable for proton treatments if all the risk factors would be accounted for.

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Objective. Proton therapy is a limited resource and is typically not available to metastatic cancer patients. Combined proton-photon therapy (CPPT), where most fractions are delivered with photons and only few with protons, represents an approach to distribute proton resources over a larger patient population. In this study, we consider stereotactic radiotherapy of multiple brain or liver metastases, and develop an approach to optimally take advantage of a single proton fraction by optimizing the proton and photon dose contributions to each individual metastasis. Approach. CPPT treatments must balance two competing goals: (1) deliver a larger dose in the proton fractions to reduce integral dose, and (2) fractionate the dose in the normal tissue between metastases, which requires using the photon fractions. Such CPPT treatments are generated by simultaneously optimizing intensity modulated proton therapy (IMPT) and intensity modulated radiotherapy (IMRT) plans based on their cumulative biologically effective dose (BED α / β ). The dose contributions of the proton and photon fractions to each individual metastasis are handled as additional optimization variables in the optimization problem. The method is demonstrated for two patients with 29 and 30 brain metastases, and two patients with 4 and 3 liver metastases. Main results. Optimized CPPT plans increase the proton dose contribution to most of the metastases, while using photons to fractionate the dose around metastases which are large or located close to critical structures. On average, the optimized CPPT plans reduce the mean brain BED 2 by 29% and the mean liver BED 4 by 42% compared to IMRT-only plans. Thereby, the CPPT plans approach the dosimetric quality of IMPT-only plans, for which the mean brain BED 2 and mean liver BED 4 are reduced by 28% and 58%, respectively, compared to IMRT-only plans. Significance. CPPT with optimized proton and photon dose contributions to individual metastases may benefit selected metastatic cancer patients without tying up major proton resources., (Creative Commons Attribution license.)

Abstract Background Neoadjuvant radio(chemo)therapy of non-metastasized, borderline resectable or unresectable locally advanced pancreatic cancer is complex and prone to cause side-effects, e.g., in gastrointestinal organs. Intensity-modulated proton therapy (IMPT) enables a high conformity to the targets while simultaneously sparing the normal tissue such that dose-escalation strategies come within reach. In this in silico feasibility study, we compared four IMPT planning strategies including robust multi-field optimization (rMFO) and a simultaneous integrated boost (SIB) for dose-escalation in pancreatic cancer patients. Methods For six pancreatic cancer patients referred for adjuvant or primary radiochemotherapy, four rMFO-IMPT-SIB treatment plans each, consisting of two or three (non-)coplanar beam arrangements, were optimized. Dose values for both targets, i.e., the elective clinical target volume [CTV, prescribed dose Dpres = 51Gy(RBE)] and the boost target [Dpres = 66Gy(RBE)], for the organs at risk as well as target conformity and homogeneity indexes, derived from the dose volume histograms, were statistically compared. Results All treatment plans of each strategy fulfilled the prescribed doses to the targets (Dpres(GTV,CTV) = 100%, D95%,(GTV,CTV) ≥ 95%, D2%,(GTV,CTV) ≤ 107%). No significant differences for the conformity index were found (p > 0.05), however, treatment plans with a three non-coplanar beam strategy were most homogenous to both targets (p

Introduction: The management of skull base malignancies continues to evolve with improvements in surgical technique, advances in radiation delivery and novel systemic agents. Methods: In this review, we aim to discuss in detail the management of common skull base pathologies which typically require multimodality therapy, focusing on the radiotherapeutic aspects of care. Results: Technological advances in the administration of radiation therapy have led to a wide variety of different treatment strategies for the treatment of skull base malignances, with outcomes summarized herein. Conclusion: Radiation treatment plays a key and critical role in the management of patients with skull base tumors. Recent advancements continue to improve the risk/benefit ratio for radiotherapy in this setting. [ABSTRACT FROM AUTHOR]

• IMPT accomplishes a significant and consistent dose reduction to OARs. • IMPT has comparable robustness compared to VMAT for oesophageal cancer. • Re-planning was required more often for IMPT compared to VMAT. 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). 19 patients with oesophageal cancer were evaluated. IMPT and VMAT plans were created on a planning 4-Dimensional CT (p4DCT) and evaluated on weekly repeated 4DCTs (r4DCT). In case of inadequate target coverage or unacceptable high dose to normal tissue, re-planning was performed. Dose distributions of the r4DCTs were warped to p4DCT, resulting in an estimated actual given dose (EAGD). Compared to VMAT, IMPT resulted in significantly lowered dose to heart, lungs, spleen, liver and kidneys. For IMPT, target coverage was adequate (after max 1 replanning) in 17/19 cases. In two cases target coverage remained insufficient. However, in one of these patients the summed dose was insufficient (due to tumor shrinkage) while weekly coverage was adequate. For the other patient the target coverage was also insufficient by VMAT, due to large anatomical changes during treatment. For VMAT, adequate target coverage was achieved in 18/19 cases without re-planning. However, for reasons of high OAR dose re-planning was required in two cases. IMPT reduces the dose to OARs significantly, while achieving adequate target coverage in the majority of patients. Re-planning was necessary for both IMPT and VMAT due to anatomical changes. [ABSTRACT FROM AUTHOR]

Purpose: To achieve a superior balance between dosimetry and the delivery efficiency of intensity‐modulated proton therapy (IMPT) using as few beams as possible in a single fraction, we optimally vary beams in different fractions. Methods: In the optimization, 400~800 feasible noncoplanar beams were included in the candidate pool. For each beam, the doses of all scanning spots covering the target volume and a margin were calculated. The fraction‐variant beam orientation optimization (FVBOO) problem was formulated to include three terms: two quadratic dose fidelity terms to penalize the deviation of planning target volume fractional dose and organs at risk (OAR) cumulative doses from prescription, respectively; an L2,1/2‐norm group sparsity term to control the number of active beams per fraction to between 1 and 4. The Fast Iterative Shrinkage‐Thresholding Algorithm (FISTA) was applied to solve this problem. FVBOO was tested on a patient with base‐of‐skull (BOS) tumor of 5 fractions (5f) and 30 fractions (30f) with an average number of active beams per fraction varying between 4 and 1. In addition, one bilateral head‐and‐neck (H&N) patient, and one esophageal cancer (ESG) patient of 30f were tested with about three active beams per fraction. The results were compared with IMPT plans that use fixed beams in each fraction. The fixed beams were selected using the group sparsity term with a fraction‐invariant BOO (FIBOO) constraint. Results: Varying beams were chosen in either the 5f or 30f FVBOO plans. While similar number of beams per fraction was selected as the FIBOO plan, the FVBOO plans were able to spare the OARs better, with an average reduction of [Dmean, Dmax] from the FIBOO plans by [0.85, 2.08] Relative Biological Effective Gy (GyRBE) in the 5f plan and [1.87, 4.06] GyRBE in the 30f plans. While reducing the number of beams per fraction in the BOS patient, a three‐beam/fraction 5f FVBOO plan performs comparably as the four‐beam FIBOO plan and a two‐beam/fraction 30f FVBOO plan still provides superior dosimetry. Conclusion: Fraction‐variant beam orientation optimization allows the utilization of a larger beam solution space for superior dose distribution in IMPT while maintaining a practical number of beams in each fraction. [ABSTRACT FROM AUTHOR]

• Compared to VMAT, IMPT is associated with less PEG placement for the treatment of OPC. • IMPT is associated with decreased acute hospitalizations compared to VMAT. • Provider-reported acute toxicities show less mucositis, dysphagia, and pain with IMPT. • Patient-reported outcomes improved with IMPT included cough and dysgeusia. • Benefits were predominantly seen in those treated definitively or with adjuvant CRT. IMPT improves normal tissue sparing compared to VMAT in treating oropharyngeal cancer (OPC). Our aim was to assess if this translates into clinical benefits. OPC patients treated with definitive or adjuvant IMPT or VMAT from 2013 to 2018 were included. All underwent prospective assessment using patient-reported-outcomes (PROs) (EORTC-QLQ-H&N35) and provider-assessed toxicities (CTCAEv4.03). End-of-treatment and pretreatment scores were compared. PEG-tube use, hospitalization, and narcotic use were retrospectively collected. Statistical analysis used the Wilcoxon Rank-Sum Test with propensity matching for PROs/provider-assessed toxicities, and t -tests for other clinical outcomes. 46 IMPT and 259 VMAT patients were included; median follow-up was 12 months (IMPT) and 30 months (VMAT). Baseline characteristics were balanced except for age (p = 0.04, IMPT were older) and smoking (p < 0.01, 10.9% IMPT >20PYs, 29.3% VMAT). IMPT was associated with lower PEG placement (OR = 0.27; 95% CI: 0.12–0.59; p = 0.001) and less hospitalization ≤60 days post-RT (OR = 0.21; 95% CI:0.07–0.6, p < 0.001), with subgroup analysis revealing strongest benefits in patients treated definitively or with concomitant chemoradiotherapy (CRT). IMPT was associated with a relative risk reduction of 22.3% for end-of-treatment narcotic use. Patients reported reduced cough and dysgeusia with IMPT (p < 0.05); patients treated definitively or with CRT also reported feeling less ill, reduced feeding tube use, and better swallow. Provider-assessed toxicities demonstrated less pain and mucositis with IMPT, but more mucosal infection. IMPT is associated with improved PROs, reduced PEG-tube placement, hospitalization, and narcotic requirements. Mucositis, dysphagia, and pain were decreased with IMPT. Benefits were predominantly seen in patients treated definitively or with CRT. [ABSTRACT FROM AUTHOR]

Background: Both plan quality and robustness were investigated through comparing some dosimetric metrics between intensity modulated proton therapy (IMPT) and helical tomotherapy based intensity modulated radiotherapy (IMRT) for cervical cancer.Methods: Both a spot-scanning robust (SRO) IMPT plan and a helical tomotherapy robust (TRO) IMRT plan were generated for each of 18 patients. In order to evaluate the quality of nominal plans without dose perturbations, planning scores (PS) on clinical target volume (CTV) and five organs at risk (OARs) based on clinical experience, and normal tissue complication probabilities (NTCP) of rectum and sigmoid were calculated based on Lyman-Kutcher-Burman (LKB) model. Dose volume histogram bands width (DVHBW) were calculated in 28 perturbed scenarios to evaluate plan robustness.Results: Compared with TRO, the average scores of SRO nominal plans were higher in target metrics [V46.8Gy, V50Gy, Conformity and Homogeneity](16.5 vs. 15.1), and in OARs metrics (60.9 vs. 53.3), including bladder [V35,V45, Dmean,D2cc], rectum [V40,V45,D2cc,Dmax], bowel [V35,V40,V45, Dmax], sigmoid [V40,Dmax] and femoral heads [V30,Dmax]. Meanwhile, NTCP calculation showed that the toxicities of rectum and sigmoid in SRO were lower than those in TRO (rectum: 2.8% vs. 4.8%, p < 0.05; sigmoid: 5.2% vs. 5.7%, p < 0.05). DVHBW in target coverage for the SRO plan was smaller than that for the TRO plan (0.6% vs. 2.1%), which means that the SRO plan generated a more robust plan in target.Conclusion: Better CTV coverage and OAR Sparing were obtained in SRO nominal plan. Based on NTCP calculation, SRO was expected to allow a small reduction in rectal toxicity. Furthermore, SRO generated a more robust plan in CTV target coverage. [ABSTRACT FROM AUTHOR]

Objective: Our goal was to investigate the performance of an open source deformable image registration package, elastix, for fast and robust contour propagation in the context of online-adaptive intensity-modulated proton therapy (IMPT) for prostate cancer.Methods: A planning and 7–10 repeat CT scans were available of 18 prostate cancer patients. Automatic contour propagation of repeat CT scans was performed using elastix and compared with manual delineations in terms of geometric accuracy and runtime. Dosimetric accuracy was quantified by generating IMPT plans using the propagated contours expanded with a 2 mm (prostate) and 3.5 mm margin (seminal vesicles and lymph nodes) and calculating dosimetric coverage based on the manual delineation. A coverage of V95% ≥ 98% (at least 98% of the target volumes receive at least 95% of the prescribed dose) was considered clinically acceptable.Results: Contour propagation runtime varied between 3 and 30 s for different registration settings. For the fastest setting, 83 in 93 (89.2%), 73 in 93 (78.5%), and 91 in 93 (97.9%) registrations yielded clinically acceptable dosimetric coverage of the prostate, seminal vesicles, and lymph nodes, respectively. For the prostate, seminal vesicles, and lymph nodes the Dice Similarity Coefficient (DSC) was 0.87 ± 0.05, 0.63 ± 0.18, and 0.89 ± 0.03 and the mean surface distance (MSD) was 1.4 ± 0.5 mm, 2.0 ± 1.2 mm, and 1.5 ± 0.4 mm, respectively.Conclusion: With a dosimetric success rate of 78.5–97.9%, this software may facilitate online adaptive IMPT of prostate cancer using a fast, free and open implementation.

Purpose: To report clinical and dosimetric characteristics of 5-fraction stereotactic ablative radiotherapy (SABR) using intensity modulated proton therapy (IMPT) for localized prostate cancer., Materials and Methods: All patients receiving IMPT SABR from 2017 to 2021 for localized prostate cancer at our institution were included. Five fractions were delivered every other day to the prostate +/- seminal vesicles [clinical target volume (CTV)] with 3 mm/3% robustness. A 4-field arrangement with 2 anterior oblique and 2 opposed lateral beams was used in most patients (97%), and most (99%) had a retroprostatic hydrogel spacer., Results: A total of 534 patients with low (14%), favorable intermediate (45%), unfavorable intermediate (36%), high (4.0%), or very high-risk (0.6%) disease are evaluated. Prescription dose was 36.25 Gy (31%), 38 Gy (38%), or 40 Gy (31%) was prescribed. Median volume percentage of CTV receiving at least 100% of prescription dose [V100% (%)] was 100% [interquartile range: 99.99-100]. Rectum V50% (%), V80% (%), and V90% (%) were significantly lower in patients who had spacer, with a mean difference of -9.70%, -6.59%, and -4.42%, respectively, compared to those who did not have spacer. Femoral head dose was lower with a 4-field arrangement. Mean differences in left and right femoral head V40% (%) were -6.99% and -10.74%, respectively., Conclusion: We provide a large, novel report of patients treated with IMPT SABR for localized prostate cancer. Four-field IMPT with hydrogel spacer provides significant sparing of rectum and femoral heads without compromising target coverage., Competing Interests: The authors have no conflicts to disclose., (© 2024 The Author(s).)

Background: To investigate the role of intensity modulated proton therapy (IMPT) compared to volumetric modulated arc therapy (VMAT) for advanced supradiaphragmatic Hodgkin's lymphoma (HL) in young female patients by assessing dosimetric features and modelling the risk of treatment related complications and radiation-induced secondary malignancies.Methods: A group of 20 cases (planned according to the involved-site approach) were retrospectively investigated in a comparative planning study. Intensity modulated proton plans (IMPT) were compared to VMAT RapidArc plans (RA). Estimates of toxicity were derived from normal tissue complication probability (NTCP) calculations with either the Lyman or the Poisson models for a number of endpoints. Estimates of the risk of secondary cancer induction were determined for lungs, breasts, esophagus and thyroid. A simple model-based selection strategy was considered as a feasibility proof for the individualized selection of patients suitable for proton therapy.Results: IMPT and VMAT plans resulted equivalent in terms of target dose distributions, both were capable to ensure high coverage and homogeneity. In terms of conformality, IMPT resulted ~ 10% better than RA plans. Concerning organs at risk, IMPT data presented a systematic improvement (highly significant) over RA for all organs, particularly in the dose range up to 20Gy. This lead to a composite average reduction of NTCP of 2.90 ± 2.24 and a reduction of 0.26 ± 0.22 in the relative risk of cardiac failures. The excess absolute risk per 10,000 patients-years of secondary cancer induction was reduced, with IMPT, of 9.1 ± 3.2, 7.2 ± 3.7 for breast and lung compared to RA. The gain in EAR for thyroid and esophagus was lower than 1. Depending on the arbitrary thresholds applied, the selection rate for proton treatment would have ranged from 5 to 75%.Conclusion: In relation to young female patients with advanced supradiaphragmatic HL, IMPT can in general offer improved dose-volume sparing of organs at risk leading to an anticipated lower risk of early or late treatment related toxicities. This would reflect also in significantly lower risk of secondary malignancies induction compared to advanced photon based techniques. Depending on the selection thresholds and with all the limits of a non-validated and very basic model, it can be anticipated that a significant fraction of patients might be suitable for proton treatments if all the risk factors would be accounted for. [ABSTRACT FROM AUTHOR]

Proton beams have been used for cancer treatment for more than 28 years, and several technological advancements have been made to achieve improved clinical outcomes by delivering more accurate and conformal doses to the target cancer cells while minimizing the dose to normal tissues. The state-of-the-art intensity modulated proton therapy is now prevailing as a major treatment technique in proton facilities worldwide, but still faces many challenges in being applied to the lung. Thus, in this article, the current status of proton therapy technique is reviewed and issues regarding the relevant uncertainty in proton therapy in the lung are summarized. [ABSTRACT FROM AUTHOR]