Radiation therapy planning with photons and protons for early and advanced breast cancer: an overview

Postoperative radiation therapy substantially decreases local relapse and moderately reduces breast cancer mortality, but can be associated with increased late mortality due to cardiovascular morbidity and secondary malignancies. Sophistication of breast irradiation techniques, including conformal radiotherapy and intensity modulated radiation therapy, has been shown to markedly reduce cardiac and lung irradiation. The delivery of more conformal treatment can also be achieved with particle beam therapy using protons. Protons have superior dose distributional qualities compared to photons, as dose deposition occurs in a modulated narrow zone, called the Bragg peak. As a result, further dose optimization in breast cancer treatment can be reasonably expected with protons. In this review, we outline the potential indications and benefits of breast cancer radiotherapy with protons. Comparative planning studies and preliminary clinical data are detailed and future developments are considered

JulianA: An automatic treatment planning platform for intensity-modulated proton therapy and its application to intra- and extracerebral neoplasms

Creating high quality treatment plans is crucial for a successful radiotherapy treatment. However, it demands substantial effort and special training for dosimetrists. Existing automated treatment planning systems typically require either an explicit prioritization of planning objectives, human-assigned objective weights, large amounts of historic plans to train an artificial intelligence or long planning times. Many of the existing auto-planning tools are difficult to extend to new planning goals. A new spot weight optimisation algorithm, called JulianA, was developed. The algorithm minimises a scalar loss function that is built only based on the prescribed dose to the tumour and organs at risk (OARs), but does not rely on historic plans. The objective weights in the loss function have default values that do not need to be changed for the patients in our dataset. The system is a versatile tool for researchers and clinicians without specialised programming skills. Extending it is as easy as adding an additional term to the loss function. JulianA was validated on a dataset of 19 patients with intra- and extracerebral neoplasms within the cranial region that had been treated at our institute. For each patient, a reference plan which was delivered to the cancer patient, was exported from our treatment database. Then JulianA created the auto plan using the same beam arrangement. The reference and auto plans were given to a blinded independent reviewer who assessed the acceptability of each plan, ranked the plans and assigned the human-/machine-made labels. The auto plans were considered acceptable in 16 out of 19 patients and at least as good as the reference plan for 11 patients. Whether a plan was crafted by a dosimetrist or JulianA was only recognised for 9 cases. The median time for the spot weight optimisation is approx. 2 min (range: 0.5 min - 7 min)

Impact of spot reduction on the effectiveness of rescanning in pencil beam scanned proton therapy for mobile tumours.

Objective. In pencil beam scanning proton therapy, individually calculated and positioned proton pencil beams, also referred to as 'spots', are used to achieve a highly conformal dose distributions to the target. Recent work has shown that this number of spots can be substantially reduced, resulting in shorter delivery times without compromising dosimetric plan quality. However, the sensitivity of spot-reduced plans to tumour motion is unclear. Although previous work has shown that spot-reduced plans are slightly more sensitive to small positioning inaccuracies of the individual pencil beams, the resulting shorter delivery times may allow for more rescanning. The aim of this study was to assess the impact of tumour motion and the effectiveness of 3D volumetric rescanning for spot-reduced treatment plans.Approach.Three liver and two lung cancer patients with non-negligible motion amplitudes were analysed. Conventional and probabilistic internal target volume definitions were used for planning considering single or multiple breathing cycles respectively. For each patient, one clinical and two spot-reduced treatment plans were created using identical field geometries. 4D dynamic dose calculations were then performed and resulting target coverage (V95%), dose homogeneity (D5%-D95%) and hot spots (D2%) evaluated for 1-25 rescans.Main results. Over all patients investigated, spot reduction reduced the number of spots by 91% in comparison to the clinical plan, reducing field delivery times by approximately 50%. This reduction, together with the substantially increased dose per spot resulting from the spot reduction process, allowed for more rescans in the same amount of time as for clinical plans and typically improved dosimetric parameters, in some cases to values better than the reference static (3D calculated) plans. However, spot-reduced plans had an increased possibility of interference with the breathing cycle, especially for simulations of perfectly repeatable breathing.Significance.For the patients analysed in this study, spot-reduced plans were found to be a valuable option to increase the efficiency of 3D volumetric rescanning for motion mitigation, if attention is paid to possible interference patterns

Ultra-fast pencil beam scanning proton therapy for locally advanced non-small-cell lung cancers: field delivery within a single breath-hold.

PURPOSE The use of motion mitigation techniques such as breath-hold can reduce the dosimetric uncertainty of lung cancer proton therapy. We studied the feasibility of pencil beam scanning (PBS) proton therapy field delivery within a single breath-hold at PSI's Gantry 2. METHODS In PBS proton therapy, the delivery time for a field is determined by the beam-on time and the dead time between proton spots (the time required to change the energy and/or lateral position). We studied ways to reduce beam-on and lateral scanning time, without sacrificing dosimetric plan quality, aiming at a single field delivery time of 15 seconds at maximum. We tested this approach on 10 lung cases with varying target volumes. To reduce the beam-on time, we increased the beam current at the isocenter by developing new beam optics for PSI's PROSCAN beamline and Gantry 2. To reduce the dead time between the spots, we used spot-reduced plan optimization. RESULTS We found that it is possible to achieve conventional fractionated (2 Gy(RBE)/fraction) and hypofractionated (6 Gy(RBE)/fraction) field delivery times within a single breath-hold (<15 sec) for a variety non-small-cell lung cancer cases. CONCLUSION In summary, the combination of spot reduction and improved beam line transmission is a promising approach for the treatment of mobile tumours within clinically achievable breath-hold durations

Treatment planning comparison for head and neck cancer between photon, proton, and combined proton-photon therapy - From a fixed beam line to an arc

BACKGROUND AND PURPOSE: This study investigates whether combined proton-photon therapy (CPPT) improves treatment plan quality compared to single-modality intensity-modulated radiation therapy (IMRT) or intensity-modulated proton therapy (IMPT) for head and neck cancer (HNC) patients. Different proton beam arrangements for CPPT and IMPT are compared, which could be of specific interest concerning potential future upright-positioned treatments. Furthermore, it is evaluated if CPPT benefits remain under inter-fractional anatomical changes for HNC treatments. MATERIAL AND METHODS: Five HNC patients with a planning CT and multiple (4-7) repeated CTs were studied. CPPT with simultaneously optimized photon and proton fluence, single-modality IMPT, and IMRT treatment plans were optimized on the planning CT and then recalculated and reoptimized on each repeated CT. For CPPT and IMPT, plans with different degrees of freedom for the proton beams were optimized. Fixed horizontal proton beam line (FHB), gantry-like, and arc-like plans were compared. RESULTS: The target coverage for CPPT without adaptation is insufficient (average V95%=88.4 %), while adapted plans can recover the initial treatment plan quality for target (average V95%=95.5 %) and organs-at-risk. CPPT with increased proton beam flexibility increases plan quality and reduces normal tissue complication probability of Xerostomia and Dysphagia. On average, Xerostomia NTCP reductions compared to IMRT are -2.7 %/-3.4 %/-5.0 % for CPPT FHB/CPPT Gantry/CPPT Arc. The differences for IMPT FHB/IMPT Gantry/IMPT Arc are + 0.8 %/-0.9 %/-4.3 %. CONCLUSION: CPPT for HNC needs adaptive treatments. Increasing proton beam flexibility in CPPT, either by using a gantry or an upright-positioned patient, improves treatment plan quality. However, the photon component is substantially reduced, therefore, the balance between improved plan quality and costs must be further determined

Treatment planning comparison for head and neck cancer between photon, proton, and combined proton-photon therapy - from a fixed beam line to an arc.

BACKGROUND AND PURPOSE This study investigates whether combined proton-photon therapy (CPPT) improves treatment plan quality compared to single-modality intensity-modulated radiation therapy (IMRT) or intensity-modulated proton therapy (IMPT) for head and neck cancer (HNC) patients. Different proton beam arrangements for CPPT and IMPT are compared, which could be of specific interest concerning potential future upright-positioned treatments. Furthermore, it is evaluated if CPPT benefits remain under inter-fractional anatomical changes for HNC treatments. MATERIAL AND METHODS Five HNC patients with a planning CT and multiple (4-7) repeated CTs were studied. CPPT with simultaneously optimized photon and proton fluence, single-modality IMPT, and IMRT treatment plans were optimized on the planning CT and then recalculated and reoptimized on each repeated CT. For CPPT and IMPT, plans with different degrees of freedom for the proton beams were optimized. Fixed horizontal proton beam line (FHB), gantry-like, and arc-like plans were compared. RESULTS The target coverage for CPPT without adaptation is insufficient (average V95%=88.4%), while adapted plans can recover the initial treatment plan quality for target (average V95%=95.5%) and organs-at-risk. CPPT with increased proton beam flexibility increases plan quality and reduces normal tissue complication probability of Xerostomia and Dysphagia. On average, Xerostomia NTCP reductions compared to IMRT are -2.7%/-3.4%/-5.0% for CPPT FHB/CPPT Gantry/CPPT Arc. The differences for IMPT FHB/IMPT Gantry/IMPT Arc are +0.8%/-0.9%/-4.3%. CONCLUSION CPPT for HNC needs adaptive treatments. Increasing proton beam flexibility in CPPT, either by using a gantry or an upright-positioned patient, improves treatment plan quality. However, the photon component is substantially reduced, therefore, the balance between improved plan quality and costs must be further determined

A fast analytical dose calculation approach for MRI-guided proton therapy.

Objective.Magnetic resonance (MR) is an innovative technology for online image guidance in conventional radiotherapy and is also starting to be considered for proton therapy as well. For MR-guided therapy, particularly for online plan adaptations, fast dose calculation is essential. Monte Carlo (MC) simulations, however, which are considered the gold standard for proton dose calculations, are very time-consuming. To address the need for an efficient dose calculation approach for MRI-guided proton therapy, we have developed a fast GPU-based modification of an analytical dose calculation algorithm incorporating beam deflections caused by magnetic fields.Approach.Proton beams (70-229 MeV) in orthogonal magnetic fields (0.5/1.5 T) were simulated using TOPAS-MC and central beam trajectories were extracted to generate look-up tables (LUTs) of incremental rotation angles as a function of water-equivalent depth. Beam trajectories are then reconstructed using these LUTs for the modified ray casting dose calculation. The algorithm was validated against MC in water, different materials and for four example patient cases, whereby it has also been fully incorporated into a treatment plan optimisation regime.Main results.Excellent agreement between analytical and MC dose distributions could be observed with sub-millimetre range deviations and differences in lateral shifts <2 mm even for high densities (1000 HU). 2%/2 mm gamma pass rates were comparable to the 0 T scenario and above 94.5% apart for the lung case. Further, comparable treatment plan quality could be achieved regardless of magnetic field strength.Significance.A new method for accurate and fast proton dose calculation in magnetic fields has been developed and successfully implemented for treatment plan optimisation

Technical note: Towards more realistic 4DCT(MRI) numerical lung phantoms.

BACKGROUND Numerical 4D phantoms, together with associated ground truth motion, offer a flexible and comprehensive data set for realistic simulations in radiotherapy and radiology in target sites affected by respiratory motion. PURPOSE We present an openly available upgrade to previously reported methods for generating realistic 4DCT lung numerical phantoms, which now incorporate respiratory ribcage motion and improved lung density representation throughout the breathing cycle. METHODS Density information of reference CTs, toget her with motion from multiple breathing cycle 4DMRIs have been combined to generate synthetic 4DCTs (4DCT(MRI)s). Inter-subject correspondence between the CT and MRI anatomy was first established via deformable image registration (DIR) of binary masks of the lungs and ribcage. Ribcage and lung motions were extracted independently from the 4DMRIs using DIR and applied to the corresponding locations in the CT after post-processing to preserve sliding organ motion. In addition, based on the Jacobian determinant of the resulting deformation vector fields, lung densities were scaled on a voxel-wise basis to more accurately represent changes in local lung density. For validating this process, synthetic 4DCTs, referred to as 4DCT(CT)s, were compared to the originating 4DCTs using motion extracted from the latter, and the dosimetric impact of the new features of ribcage motion and density correction were analyzed using pencil beam scanned proton 4D dose calculations. RESULTS Lung density scaling led to a reduction of maximum mean lung Hounsfield units (HU) differences from 45 to 12 HU when comparing simulated 4DCT(CT)s to their originating 4DCTs. Comparing 4D dose distributions calculated on the enhanced 4DCT(CT)s to those on the original 4DCTs yielded 2%/2 mm gamma pass rates above 97% with an average improvement of 1.4% compared to previously reported phantoms. CONCLUSIONS A previously reported 4DCT(MRI) workflow has been successfully improved and the resulting numerical phantoms exhibit more accurate lung density representations and realistic ribcage motion

A unified generation-registration framework for improved MR-based CT synthesis in proton therapy.

BACKGROUND The use of magnetic resonance (MR) imaging for proton therapy treatment planning is gaining attention as a highly effective method for guidance. At the core of this approach is the generation of computed tomography (CT) images from MR scans. However, the critical issue in this process is accurately aligning the MR and CT images, a task that becomes particularly challenging in frequently moving body areas, such as the head-and-neck. Misalignments in these images can result in blurred synthetic CT (sCT) images, adversely affecting the precision and effectiveness of the treatment planning. PURPOSE This study introduces a novel network that cohesively unifies image generation and registration processes to enhance the quality and anatomical fidelity of sCTs derived from better-aligned MR images. METHODS The approach synergizes a generation network (G) with a deformable registration network (R), optimizing them jointly in MR-to-CT synthesis. This goal is achieved by alternately minimizing the discrepancies between the generated/registered CT images and their corresponding reference CT counterparts. The generation network employs a UNet architecture, while the registration network leverages an implicit neural representation (INR) of the displacement vector fields (DVFs). We validated this method on a dataset comprising 60 head-and-neck patients, reserving 12 cases for holdout testing. RESULTS Compared to the baseline Pix2Pix method with MAE 124.95 30.74 HU, the proposed technique demonstrated 80.98 7.55 HU. The unified translation-registration network produced sharper and more anatomically congruent outputs, showing superior efficacy in converting MR images to sCTs. Additionally, from a dosimetric perspective, the plan recalculated on the resulting sCTs resulted in a remarkably reduced discrepancy to the reference proton plans. CONCLUSIONS This study conclusively demonstrates that a holistic MR-based CT synthesis approach, integrating both image-to-image translation and deformable registration, significantly improves the precision and quality of sCT generation, particularly for the challenging body area with varied anatomic changes between corresponding MR and CT

Using a reduced spot size for intensity-modulated proton therapy potentially improves salivary gland-sparing in oropharyngeal cancer

Purpose: To investigate whether intensity-modulated proton therapy with a reduced spot size (rsIMPT) could further reduce the parotid and submandibular gland dose compared with previously calculated IMPT plans with a larger spot size. In addition, it was investigated whether the obtained dose reductions would theoretically translate into a reduction of normal tissue complication probabilities (NTCPs). Methods: Ten patients with N0 oropharyngeal cancer were included in a comparative treatment planning study. Both IMPT plans delivered simultaneously 70 Gy to the boost planning target volume (PTV) and 54 Gy to the elective nodal PTV. IMPT and rsIMPT used identical three-field beam arrangements. In the IMPT plans, the parotid and submandibular salivary glands were spared as much as possible. rsIMPT plans used identical dose-volume objectives for the parotid glands as those used by the IMPT plans, whereas the objectives for the submandibular glands were tightened further. NTCPs were calculated for salivary dysfunction and xerostomia. Results: Target coverage was similar for both IMPT techniques, whereas rsIMPT clearly improved target conformity. The mean doses in the parotid glands and submandibular glands were significantly lower for three-field rsIMPT (14.7 Gy and 46.9 Gy, respectively) than for three-field IMPT (16.8 Gy and 54.6 Gy, respectively). Hence, rsIMPT significantly reduced the NTCP of patient-rated xerostomia and parotid and contralateral submandibular salivary flow dysfunction (27%, 17%, and 43% respectively) compared with IMPT (39%, 20%, and 79%, respectively). In addition, mean dose values in the sublingual glands, the soft palate and oral cavity were also decreased. Obtained dose and NTCP reductions varied per patient. Conclusions: rsIMPT improved sparing of the salivary glands and reduced NTCP for xerostomia and parotid and submandibular salivary dysfunction, while maintaining similar target coverage results. It is expected that rsIMPT improves quality of life during and after radiotherapy treatment.</p