Roadmap: proton therapy physics and biology Paganetti, Harald; Beltran, Chris; Both, Stefan ...
Physics in medicine & biology,
02/2021, Letnik:
66, Številka:
5
Journal Article
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The treatment of cancer with proton radiation therapy was first suggested in 1946 followed by the first treatments in the 1950s. As of 2020, almost 200 000 patients have been treated with proton ...beams worldwide and the number of operating proton therapy (PT) facilities will soon reach one hundred. PT has long moved from research institutions into hospital-based facilities that are increasingly being utilized with workflows similar to conventional radiation therapy. While PT has become mainstream and has established itself as a treatment option for many cancers, it is still an area of active research for various reasons: the advanced dose shaping capabilities of PT cause susceptibility to uncertainties, the high degrees of freedom in dose delivery offer room for further improvements, the limited experience and understanding of optimizing pencil beam scanning, and the biological effect difference compared to photon radiation. In addition to these challenges and opportunities currently being investigated, there is an economic aspect because PT treatments are, on average, still more expensive compared to conventional photon based treatment options. This roadmap highlights the current state and future direction in PT categorized into four different themes, 'improving efficiency', 'improving planning and delivery', 'improving imaging', and 'improving patient selection'.
Purpose:
Target sites affected by organ motion require a time resolved (4D) dose calculation. Typical 4D dose calculations use 4D-CT as a basis. Unfortunately, 4D-CT images have the disadvantage of ...being a “snap-shot” of the motion during acquisition and of assuming regularity of breathing. In addition, 4D-CT acquisitions involve a substantial additional dose burden to the patient making many, repeated 4D-CT acquisitions undesirable. Here the authors test the feasibility of an alternative approach to generate patient specific 4D-CT data sets.
Methods:
In this approach motion information is extracted from 4D-MRI. Simulated 4D-CT data sets which the authors call 4D-CT(MRI) are created by warping extracted deformation fields to a static 3D-CT data set. The employment of 4D-MRI sequences for this has the advantage that no assumptions on breathing regularity are made, irregularities in breathing can be studied and, if necessary, many repeat imaging studies (and consequently simulated 4D-CT data sets) can be performed on patients and/or volunteers. The accuracy of 4D-CT(MRI)s has been validated by 4D proton dose calculations. Our 4D dose algorithm takes into account displacements as well as deformations on the originating 4D-CT/4D-CT(MRI) by calculating the dose of each pencil beam based on an individual time stamp of when that pencil beam is applied. According to corresponding displacement and density-variation-maps the position and the water equivalent range of the dose grid points is adjusted at each time instance.
Results:
4D dose distributions, using 4D-CT(MRI) data sets as input were compared to results based on a reference conventional 4D-CT data set capturing similar motion characteristics. Almost identical 4D dose distributions could be achieved, even though scanned proton beams are very sensitive to small differences in the patient geometry. In addition, 4D dose calculations have been performed on the same patient, but using 4D-CT(MRI) data sets based on variable breathing patterns to show the effect of possible irregular breathing on active scanned proton therapy. Using a 4D-CT(MRI), including motion irregularities, resulted in significantly different proton dose distributions.
Conclusions:
The authors have demonstrated that motion information from 4D-MRI can be used to generate realistic 4D-CT data sets on the basis of a single static 3D-CT data set. 4D-CT(MRI) presents a novel approach to test the robustness of treatment plans in the circumstance of patient motion.
We report on a comparative dosimetrical study between deep inspiration breath hold (DIBH) and shallow breathing (SB) in prone crawl position for photon and proton radiotherapy of whole breast (WB) ...and locoregional lymph node regions, including the internal mammary chain (LN_MI). We investigate the dosimetrical effects of DIBH in prone crawl position on organs-at-risk for both photon and proton plans. For each modality, we further estimate the effects of lung and heart doses on the mortality risks of different risk profiles of patients. Thirty-one patients with invasive carcinoma of the left breast and pathologically confirmed positive lymph node status were included in this study. DIBH significantly decreased dose to heart for photon and proton radiotherapy. DIBH also decreased lung doses for photons, while increased lung doses were observed using protons because the retracting heart is displaced by low-density lung tissue. For other organs-at-risk, DIBH resulted in significant dose reductions using photons while minor differences in dose deposition between DIBH and SB were observed using protons. In patients with high risks for cardiac and lung cancer mortality, average thirty-year mortality rates from radiotherapy-related cardiac injury and lung cancer were estimated at 3.12% (photon DIBH), 4.03% (photon SB), 1.80% (proton DIBH) and 1.66% (proton SB). The radiation-related mortality risk could not outweigh the ~ 8% disease-specific survival benefit of WB + LN_MI radiotherapy in any of the assessed treatments.
Skull base chordomas are rare and heterogeneously behaving tumors. Though still classified as benign they can grow rapidly, are locally aggressive, and have the potential to metastasize. To adapt the ...treatment to the specific needs of patients at higher risk of recurrence, a pre-proton therapy prognostic grading system would be useful. The aim of this retrospective analysis is to assess prognostic factors and the "Sekhar Grading System for Cranial Chordomas" (SGSCC) by evaluating the larger cohort of patients treated at our institution as to determine its reproducibility and ultimately to ensure more risk adapted local treatments for these challenging tumors.
We analyzed 142 patients treated for skull base chordomas between 2004 and 2016. We focused the analysis on the 5 criteria proposed for the SGSCC (tumor size, number of anatomic regions and vessels involved, intradural invasion, as well as recurrence after prior treatment) and classified our patients according to their score (based on the above mentioned criteria) into three prognostic groups, low-risk, intermediate-risk and high-risk. The three groups were then analyzed in regards of local control, local recurrence-free survival and overall survival.
The median follow up was 52 months (range, 3-152). We observed 34 (24%) patients with a local recurrence, resulting in a local control of 75% at 5 years. Overall survival was 83% at 5 years, 12 (9%) patients had died due to local progression. When split into the three prognostic groups according to the SGSCC the observed local control was 90, 72 and 64% (p = 0.07) in the low-, intermediate- and high-risk group, respectively. A similar correlation was observed for local recurrence-free survival with 93, 89 and 66% (p = 0.05) and for overall survival with 89, 83 and 76% (p = 0.65) for the same prognostic groups.
After splitting our patient cohort into the three SGSCC risk groups, we found a trend towards better outcome for those patients with lower as opposed to higher scores. These results suggest that this prognostic grading system published by Sekhar et al. could be integrated in the management decision-tree for patients with skull base chordoma.
The presented work has two goals. First, to demonstrate the feasibility of accurately characterizing a proton radiation field at treatment head exit for Monte Carlo dose calculation of active ...scanning patient treatments. Second, to show that this characterization can be done based on measured depth dose curves and spot size alone, without consideration of the exact treatment head delivery system. This is demonstrated through calibration of a Monte Carlo code to the specific beam lines of two institutions, Massachusetts General Hospital (MGH) and Paul Scherrer Institute (PSI). Comparison of simulations modeling the full treatment head at MGH to ones employing a parameterized phase space of protons at treatment head exit reveals the adequacy of the method for patient simulations. The secondary particle production in the treatment head is typically below 0.2% of primary fluence, except for low-energy electrons (<0.6 MeV for 230 MeV protons), whose contribution to skin dose is negligible. However, there is significant difference between the two methods in the low-dose penumbra, making full treatment head simulations necessary to study out-of-field effects such as secondary cancer induction. To calibrate the Monte Carlo code to measurements in a water phantom, we use an analytical Bragg peak model to extract the range-dependent energy spread at the two institutions, as this quantity is usually not available through measurements. Comparison of the measured with the simulated depth dose curves demonstrates agreement within 0.5 mm over the entire energy range. Subsequently, we simulate three patient treatments with varying anatomical complexity (liver, head and neck and lung) to give an example how this approach can be employed to investigate site-specific discrepancies between treatment planning system and Monte Carlo simulations.
•Tumor movements smaller than 5 mm do not require motion mitigation.•Volumetric rescanning improve CTV dose coverage for intermediate tumor motions (5–10 mm) using a dense spot grid, whilst being ...more time efficient than respiratory gating.•Respiratory gating does not necessarily reduce dose to normal tissues for intermediate tumor motions.•Respiratory gating combined with volumetric rescanning improve CTV dose coverage for tumor motions larger than 10 mm using a dense or sparse spot grid.•A denser spot grid gives better CTV dose coverage.•Combined rescanning and gating treatments of moving tumors with proton pencil beam can be used effectively and efficiently.
Respiratory motion during proton therapy can severely degrade dose distributions, particularly due to interplay effects when using pencil beam scanning. Combined rescanning and gating treatments for moving tumors mitigates dose degradation, but at the cost of increased treatment delivery time. The objective of this study was to identify the time efficiency of these dose degradation-motion mitigation strategies for different range of motions.
Seventeen patients with thoracic or abdominal tumors were studied. Tumor motion amplitudes ranged from 2–30 mm. Deliveries using different combinations of rescanning and gating were simulated with a dense dose spot grid (4 × 4 × 2.5 mm3) for all patients and a sparse dose spot grid (8 × 8 × 5 mm3) for six patients with larger tumor movements (>8 mm). The resulting plans were evaluated in terms of CTV coverage and time efficiency.
Based on the studied patient cohort, it has been shown that for amplitudes up to 5 mm, no motion mitigation is required with a dense spot grid. For amplitudes between 5 and 10 mm, volumetric rescanning should be applied while maintaining a 100% duty cycle when using a dense spot grid. Although gating could be envisaged to reduce the target volume for intermediate motion, it has been shown that the dose to normal tissues would only be reduced marginally. Moreover, the treatment time would increase. Finally, for larger motion amplitudes, both volumetric rescanning and respiratory gating should be applied with both spot grids. In addition, it has been shown that a dense spot grid delivers better CTV dose coverage than a sparse dose grid.
Volumetric rescanning and/or respiratory gating can be used in order to effectively and efficiently mitigate dose degradation due to tumor movement.
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