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

Universal and dynamic ridge filter for pencil beam scanning particle therapy: a novel concept for ultra-fast treatment delivery.

Objective.In pencil beam scanning particle therapy, a short treatment delivery time is paramount for the efficient treatment of moving targets with motion mitigation techniques (such as breath-hold, rescanning, and gating). Energy and spot position change time are limiting factors in reducing treatment time. In this study, we designed a universal and dynamic energy modulator (ridge filter, RF) to broaden the Bragg peak, to reduce the number of energies and spots required to cover the target volume, thus lowering the treatment time.Approach. Our RF unit comprises two identical RFs placed just before the isocenter. Both RFs move relative to each other, changing the Bragg peak's characteristics dynamically. We simulated different Bragg peak shapes with the RF in Monte Carlo simulation code (TOPAS) and validated them experimentally. We then delivered single-field plans with 1 Gy/fraction to different geometrical targets in water, to measure the dose delivery time using the RF and compare it with the clinical settings.Main results.Aligning the RFs in different positions produces different broadening in the Bragg peak; we achieved a maximum broadening of 2.5 cm. With RF we reduced the number of energies in a field by more than 60%, and the dose delivery time by 50%, for all geometrical targets investigated, without compromising the dose distribution transverse and distal fall-off.Significance. Our novel universal and dynamic RF allows for the adaptation of the Bragg peak broadening for a spot and/or energy layer based on the requirement of dose shaping in the target volume. It significantly reduces the number of energy layers and spots to cover the target volume, and thus the treatment time. This RF design is ideal for ultra-fast treatment delivery within a single breath-hold (5-10 s), efficient delivery of motion mitigation techniques, and small animal irradiation with ultra-high dose rates (FLASH)

Combined proton-photon therapy for non-small cell lung cancer

PURPOSE Advanced non-small cell lung cancer (NSCLC) is still a challenging indication for conventional photon radiotherapy. Proton therapy has the potential to improve outcomes, but proton treatment slots remain a limited resource despite an increasing number of proton therapy facilities. This work investigates the potential benefits of optimally combined proton-photon therapy delivered using a fixed horizontal proton beam line in combination with a photon Linac, which could increase accessibility to proton therapy for such a patient cohort. MATERIALS AND METHODS A treatment planning study has been conducted on a patient cohort of seven advanced NSCLC patients. Each patient had a planning computed tomography scan (CT) and multiple repeated CTs from three different days and for different breath-holds on each day. Treatment plans for combined proton-photon therapy (CPPT) were calculated for individual patients by optimizing the combined cumulative dose on the initial planning CT only (non-adapted) as well as on each daily CT respectively (adapted). The impact of inter-fractional changes and/or breath-hold variability was then assessed on the repeat breath-hold CTs. Results were compared to plans for IMRT or IMPT alone, as well as against combined treatments assuming a proton gantry. Plan quality was assessed in terms of dosimetric, robustness and NTCP metrics. RESULTS Combined treatment plans improved plan quality compared to IMRT treatments, especially in regard to reductions of low and medium doses to organs at risk (OARs), which translated into lower NTCP estimates for three side effects. For most patients, combined treatments achieved results close to IMPT-only plans. Inter-fractional changes impact mainly the target coverage of combined and IMPT treatments, while OARs doses were less affected by these changes. With plan adaptation however, target coverage of combined treatments remained high even when taking variability between breath-holds into account. CONCLUSIONS Optimally combined proton-photon plans improve treatment plan quality compared to IMRT only, potentially reducing the risk of toxicity while also allowing to potentially increase accessibility to proton therapy for NSCLC patients

Dosimetric comparison of autocontouring techniques for online adaptive proton therapy.

anatomical and daily set-up uncertainties impede high precision delivery of proton therapy. With online adaptation, the daily plan is reoptimized on an image taken shortly before the treatment, reducing these uncertainties and, hence, allowing a more accurate delivery. This reoptimization requires target and organs-at-risk (OAR) contours on the daily image, which need to be delineated automatically since manual contouring is too slow. Whereas multiple methods for autocontouring exist, none of them are fully accurate, which affects the daily dose. This work aims to quantify the magnitude of this dosimetric effect for four contouring techniques.

Approach: plans reoptimized on automatic contours are compared with plans reoptimized on manual contours. The methods include rigid and deformable registration (DIR), deep-learning based segmentation and patient-specific segmentation.

Results: it was found that independently of the contouring method, the dosimetric influence of using automatic OAR contours is small ( 5% prescribed dose in most cases), indicating that manual verification of that contour remains necessary. However, when compared to non-adaptive therapy, the dose differences caused by automatically contouring the target were small and target coverage was improved, especially for DIR.

Significance: the results show that manual adjustment of OARs is rarely necessary and that several autocontouring techniques are directly usable. Contrarily, manual adjustment of the target is important. This allows prioritizing tasks during time-critical online adaptive proton therapy and therefore supports its further clinical implementation

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

Purpose: A major burden of introducing an online daily adaptive proton therapy (DAPT) workflow is the time and resources needed to correct the daily propagated contours. In this study, we evaluated the dosimetric impact of neglecting the online correction of the propagated contours in a DAPT workflow.Material and methods: For five NSCLC patients with nine repeated deep-inspiration breath-hold CTs, proton therapy plans were optimised on the planning CT to deliver 60 Gy-RBE in 30 fractions. All repeated CTs were registered with six different clinically used deformable image registration (DIR) algorithms to the corresponding planning CT. Structures were propagated rigidly and with each DIR algorithm and reference structures were contoured on each repeated CT. DAPT plans were optimised with the uncorrected, propagated structures (propagated DAPT doses) and on the reference structures (ideal DAPT doses), nonadapted doses were recalculated on all repeated CTs.Results: Due to anatomical changes occurring during the therapy, the clinical target volume (CTV) coverage of the non-adapted doses reduces on average by 9.7% (V95) compared to an ideal DAPT doses. For the propagated DAPT doses, the CTV coverage was always restored (average differences in the CTV V95 &lt; 1% compared to the ideal DAPT doses). Hotspots were always reduced with any DAPT approach.Conclusion: For the patients presented here, a benefit of online DAPT was shown, even if the daily optimisation is based on propagated structures with some residual uncertainties. However, a careful (offline) structure review is necessary and corrections can be included in an offline adaption.(c) 2021 The Author(s). Published by Elsevier B.V. Radiotherapy and Oncology 159 (2021) 136-143 This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).</p

4DMRI-based investigation on the interplay effect for pencil beam scanning proton therapy of pancreatic cancer patients

Background: Time-resolved volumetric magnetic resonance imaging (4DMRI) offers the potential to analyze 3D motion with high soft-tissue contrast without additional imaging dose. We use 4DMRI to investigate the interplay effect for pencil beam scanning (PBS) proton therapy of pancreatic cancer and to quantify the dependency of residual interplay effects on the number of treatment fractions. Methods: Based on repeated 4DMRI datasets for nine pancreatic cancer patients, synthetic 4DCTs were generated by warping static 3DCTs with 4DMRI deformation vector fields. 4D dose calculations for scanned proton therapy were performed to quantify the interplay effect by CTV coverage (v95) and dose homogeneity (d5/d95) for incrementally up to 28 fractions. The interplay effect was further correlated to CTV motion characteristics. For quality assurance, volume and mass conservation were evaluated by Jacobian determinants and volume-density comparisons. Results: For the underlying patient cohort with CTV motion amplitudes &lt; 15 mm, we observed significant correlations between CTV motion amplitudes and both the length of breathing cycles and the interplay effect. For individual fractions, tumor underdosage down to v95 = 70% was observed with pronounced dose heterogeneity (d5/d95 = 1.3). For full × 28 fractionated treatments, we observed a mitigation of the interplay effect with increasing fraction numbers. On average, after seven fractions, a CTV coverage with 95–107% of the prescribed dose was reached with sufficient dose homogeneity. For organs at risk, no significant differences were found between the static and accumulated dose plans for 28 fractions. Conclusion: Intrafractional organ motion exhibits a large interplay effect for PBS proton therapy of pancreatic cancer. The interplay effect correlates with CTV motion, but can be mitigated efficiently by fractionation, mainly due to different breathing starting phases in fractionated treatments. For hypofractionated treatments, a further restriction of motion may be required. Repeated 4DMRI measurements are a viable tool for pre- and post-treatment evaluations of the interplay effect

In the context of radiosurgery - pros and cons of rescanning as a solution for treating moving targets with scanned particle beams

The treatment of mobile targets with scanned particle beams is challenging, and the effects of motion will be especially pronounced in hypo-fractionated treatment regimes due to the lack of statistical smoothing through fractionation and the prolonged delivery times per session. Therefore, motion mitigation techniques will play a major role for radiosurgery approaches. This article concentrates on the motion mitigation technique called rescanning. It alludes the existence of many scanning/rescanning flavors and raises awareness of the importance of an optimized flavor choice. Furthermore, it is discussed that rescanning can compensate for the lack of statistical wash-out, target dose conformity, however, will remain degraded. Therefore, especially in the context of radiosurgery, rescanning should be combined with other motion mitigation techniques like breath hold, gating and/or tracking

Automatic lung segmentation of magnetic resonance images: A new approach applied to healthy volunteers undergoing enhanced Deep-Inspiration-Breath-Hold for motion-mitigated 4D proton therapy of lung tumors.

BACKGROUND AND PURPOSE Respiratory suppression techniques represent an effective motion mitigation strategy for 4D-irradiation of lung tumors with protons. A magnetic resonance imaging (MRI)-based study applied and analyzed methods for this purpose, including enhanced Deep-Inspiration-Breath-Hold (eDIBH). Twenty-one healthy volunteers (41-58 years) underwent thoracic MR scans in four imaging sessions containing two eDIBH-guided MRIs per session to simulate motion-dependent irradiation conditions. The automated MRI segmentation algorithm presented here was critical in determining the lung volumes (LVs) achieved during eDIBH. MATERIALS AND METHODS The study included 168 MRIs acquired under eDIBH conditions. The lung segmentation algorithm consisted of four analysis steps: (i) image preprocessing, (ii) MRI histogram analysis with thresholding, (iii) automatic segmentation, (iv) 3D-clustering. To validate the algorithm, 46 eDIBH-MRIs were manually contoured. Sørensen-Dice similarity coefficients (DSCs) and relative deviations of LVs were determined as similarity measures. Assessment of intrasessional and intersessional LV variations and their differences provided estimates of statistical and systematic errors. RESULTS Lung segmentation time for 100 2D-MRI planes was ∼ 10 s. Compared to manual lung contouring, the median DSC was 0.94 with a lower 95 % confidence level (CL) of 0.92. The relative volume deviations yielded a median value of 0.059 and 95 % CLs of -0.013 and 0.13. Artifact-based volume errors, mainly of the trachea, were estimated. Estimated statistical and systematic errors ranged between 6 and 8 %. CONCLUSIONS The presented analytical algorithm is fast, precise, and readily available. The results are comparable to time-consuming, manual segmentations and other automatic segmentation approaches. Post-processing to remove image artifacts is under development

Multi-breath 4DCT images of lung cancer patients

&lt;p&gt;&lt;strong&gt;Multi-breath 4DCT images of six non-small cell lung cancer (NSCLC) patients.&lt;/strong&gt;&lt;/p&gt;&lt;p&gt;Breathing motion has been transferred across longitudinal imaging to generate new 4DCT images sampling five consecutive breaths.&lt;/p&gt;&lt;p&gt;This dataset is the result of processing six subjects selected from the 4D-Lung dataset published in The Cancer Imaging Archive: &lt;a href="https://doi.org/10.7937/K9/TCIA.2016.ELN8YGLE"&gt;https://doi.org/10.7937/K9/TCIA.2016.ELN8YGLE &lt;/a&gt;Hugo et al. (2016).&lt;/p&gt;&lt;p&gt;Data generated within the project "New concept for adaptive real time tumour tracking" funded by the Swiss National Science Foundation (SNSF) under grant agreement 200021_185082: &lt;a href="https://data.snf.ch/grants/grant/185082"&gt;https://data.snf.ch/grants/grant/185082&lt;/a&gt;&nbsp;&lt;/p&gt;&lt;p&gt;&nbsp;&lt;/p&gt

Beam properties within the momentum acceptance of a clinical gantry beamline for proton therapy

&lt;p&gt;Publicly accessible data associated with the publication:&nbsp;&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Beam properties within the momentum acceptance of aclinical gantry beamline for proton therapy&lt;/strong&gt;.&nbsp;&lt;/p&gt;&lt;p&gt;AC Giovannelli, V Maradia, D Meer, S Safai, S Psoroulas, M Togno, C Bula, DC Weber, AJ Lomax, G Fattori. Med Phys 2022;49(3):1417-1431. &lt;a href="https://doi.org/10.1002/mp.15449"&gt;https://doi.org/10.1002/mp.15449&lt;/a&gt;&lt;/p&gt;&lt;p&gt;Data generated within the project "New concept for adaptive real time tumour tracking" funded by the Swiss National Science Foundation (SNSF) under grant agreement 200021_185082: &lt;a href="https://data.snf.ch/grants/grant/185082"&gt;https://data.snf.ch/grants/grant/185082&lt;/a&gt;&nbsp;&lt;/p&gt;&lt;p&gt;&nbsp;&lt;/p&gt