Whole breast proton irradiation for maximal reduction of heart dose in breast cancer patients

PURPOSE: In left-sided breast cancer radiotherapy, tangential intensity modulated radiotherapy combined with breath-hold enables a dose reduction to the heart and left anterior descending (LAD) coronary artery. Aim of this study was to investigate the added value of intensity modulated proton therapy (IMPT) with regard to decreasing the radiation dose to these structures. METHODS: In this comparative planning study, four treatment plans were generated in 20 patients: an IMPT plan and a tangential IMRT plan, both with breath-hold and free-breathing. At least 97 % of the target volume had to be covered by at least 95 % of the prescribed dose in all cases. Specifically with respect to the heart, the LAD, and the target volumes, we analyzed the maximum doses, the mean doses, and the volumes receiving 5-30 Gy. RESULTS: As compared to IMRT, IMPT resulted in significant dose reductions to the heart and LAD-region even without breath-hold. In the majority of the IMPT cases, a reduction to almost zero to the heart and LAD-region was obtained. IMPT treatment plans yielded the lowest dose to the lungs. CONCLUSIONS: With IMPT the dose to the heart and LAD-region could be significantly decreased compared to tangential IMRT with breath-hold. The clinical relevance should be assessed individually based on the baseline risk of cardiac complications in combination with the dose to organs at risk. However, as IMPT for breast cancer is currently not widely available, IMPT should be reserved for patients remaining at high risk for major coronary events

Emerging technologies in proton therapy

An increasing number of proton therapy facilities are being planned and built at hospital based centers. Most facilities are employing traditional dose delivery methods. A second generation of dose application techniques, based on pencil beam scanning, is slowly being introduced into the commercially available proton therapy systems. New developments in accelerator physics are needed to accommodate and fully exploit these new techniques. At the same time new developments such as the development of small cyclotrons, Dielectric Wall Accelerator (DWA) and laser driven systems, aim for smaller, single room treatment units. In general the benefits of proton therapy could be exploited optimally when achieving a higher level in accuracy, beam energy, beam intensity, safety and system reliability. In this review an overview of the current developments will be given followed by a discussion of upcoming new technologies and needs, like increase of energy, on-line MRI and proton beam splitting for independent uses of treatment rooms

Towards FLASH proton therapy: the impact of treatment planning and machine characteristics on achievable dose rates.

This study aimed at evaluating spatially varying instantaneous dose rates for different intensity-modulated proton therapy (IMPT) planning strategies and delivery scenarios, and comparing these with FLASH dose rates (>40 Gy/s). In order to quantify dose rates in three-dimensions, we proposed the 'dose-averaged dose rate' (DADR) metric, defined for each voxel as the dose-weighted mean of the instantaneous dose rates of all spots (i.e., pencil beams). This concept was applied to four head-and-neck cases, each planned with clinical (4 fields) and various spot-reduced IMPT techniques: 'standard' (4 fields), 'arc' (120 fields) and 'arc-shoot-through' (120 fields; 229 MeV only). For all plans, different delivery scenarios were simulated: constant beam intensity, variable beam intensity for a clinical Varian ProBeam system, varied per energy layer or per spot, and theoretical spot-wise variable beam intensity (i.e., no monitor/safety limitations). DADR distributions were calculated assuming 2-Gy or 6-Gy fractions. Spot-reduced plans contained 17-52 times fewer spots than clinical plans, with no deterioration of plan quality. For the clinical plans, the mean DADR in normal tissue for 2-Gy fractionation was 1.7 Gy/s (median over all patients) at maximum, whereas in standard spot-reduced plans it was 0.7, 4.4, 7.1, and 12.1 Gy/s, for the constant, energy-layer-wise, spot-wise, and theoretical spot-wise delivery scenarios, respectively. Similar values were observed for arc plans. Arc-shoot-through planning resulted in DADR values of 3.0, 6.0, 14.1, and 24.4 Gy/s, for the abovementioned scenarios. Hypofractionation (3×) generally resulted in higher dose rates, up to 73.2 Gy/s for arc-shoot-through plans. The DADR was inhomogeneously distributed with highest values at beam entrance and at the Bragg peak. FLASH dose rates were not achieved for conventional planning and clinical spot-scanning machines. As such, increased spot-wise beam intensities, spot-reduced planning, hypofractionation and arc-shoot-through plans were required to achieve FLASH compatible dose rates

A novel method of emittance matching to increase beam transmission for cyclotron-based proton therapy facilities: simulation study

In proton therapy, high dose rates can reduce treatment delivery times, allowing for efficient mitigation of tumor motion and increased patient throughput. With cyclotrons however, high dose rates are difficult to achieve for low-energies as, typically, the emittance after the degrader is matched in both transversal planes using circular collimators, which does not provide an optimal matching to the acceptance of the following beamline. Transmission can however be substantially improved by transporting maximum acceptable emittances in both orthogonal planes, but at the cost of gantry angle-dependent beam shapes at isocenter. Here we demonstrate that equal emittances in both planes can be recovered at the gantry entrance using a thin scattering foil, thus ensuring gantry angle-independent beam shapes at the isocenter. We demonstrate in simulation that low-energy beam transmission can be increased by a factor of 3 using this approach compared to the currently used beam optics, whilst gantry angle-independent beam shapes are preserved. We expect that this universal approach could also bring a similar trans-mission improvement in other cyclotron-based proton therapy facilities

BATH AND SHOWER EFFECTS IN THE RAT PAROTID GLAND EXPLAIN INCREASED RELATIVE RISK OF PAROTID GLAND DYSFUNCTION AFTER INTENSITY-MODULATED RADIOTHERAPY

Purpose: To assess in a rat model whether adding a subtolerance dose in a region adjacent to a high-dose irradiated subvolume of the parotid gland influences its response (bath-and-shower effect). Methods and Materials: Irradiation of the whole, cranial 50%, and/or the caudal 50% of the parotid glands of Wistar rats was performed using 150-MeV protons. To determine suitable (i.e., subtolerance) dose levels for a bath-dose, both whole parotid glands were irradiated with 5 to 25 Gy. Subsequently groups of Wistar rats received 30 Gy to the caudal 50% (shower) and 0 to 10 Gy to the cranial 50% (bath) of both parotid glands. Stimulated saliva flow rate (function) was measured before and up to 240 days after irradiation. Results : Irradiation of both glands up to a dose of 10 Gy did not result in late loss of function and is thus regarded subtolerance. Addition of a dose bath of I to 10 Gy to a high-dose in the caudal 50% of the glands resulted in enhanced function loss. Conclusion: Similar to the spinal cord, the parotid gland demonstrates a bath and shower effect, which may explain the less-than-expected sparing of function after IMRT. (C) 2009 Elsevier Inc

New Gantry Beam Optics Solution for Minimising Treatment Time in Cyclotron-based Proton Therapy Facilities

Treatment delivery time in proton therapy depends on beam-on time and the time required to change energy layers and/or lateral position. For cyclotron-based facilities, low energy beams (100-70 MeV) are inefficiently transported through beamlines due to their large emittance after the degrader (~400 pi*mm*mrad 2-sigma emittance), whereas the beamline and Gantry can only transport small emittances (e.g. 30 pi*mm*mrad for PSI Gantry 2) resulting in a low dose rate at the patient and increased beam-on time. In this work, we aim to maximize the emittance transported through the gantry for low energy beams. By choosing a small divergence, but large beam size, at the gantry entrance, it is possible to transport higher emittances through the gantry without compromising transmission. Additionally, in order to retrieve small beam sizes at the patient, we propose a 2:1 imaging of the gantry beam optics between the gantry coupling point and the patient. This concept has been experimentally validated on Gantry 2 at PSI. A beam with an emittance of 90 pi*mm*mrad and ~60% transmission was transported through the gantry. As we are transporting only a narrow part of the large Gaussian beam after the degrader, this 3 times higher emittance corresponds to ~3 times more transported particles. With this, treatment times for example cases (lung and liver) have been estimated to reduce by a factor of 2 to 3. Such a beam optic could therefore have substantial potential for reducing treatment times, and be of particular advantage for the treatment of moving targets

A Novel Beam Optics Concept to Maximize the Transmission Through Cyclotron-based Proton Therapy Gantries

Most of the conventional beam optics of cyclotron-based proton gantries were designed to provide point-to-point focus in both planes with an imaging factor between 1 and 2 from the entrance of the gantry to the patient. This means that a small beam size at the gantry entrance is required to achieve the required small beam size at the patient. Due to the typically used beam emittance, this in turn results in large beam divergence at the gantry entrance, increasing the possibility of beam losses along the gantry as the beam envelope gets close to the apertures. To maximize transmission through the gantry, we propose a novel beam optics concept using 3:1 imaging. It reduces the beam divergence at the gantry entrance by factor 3 while still achieving a small beam size at the patient. The beam envelope is better controlled and keeps clear of the apertures compared to the 1:1 or 1:2 imaging beam envelope. For PSI Gantry 2, the novel 3:1 imaging beam optics increase the proton beam transmission for lower energies by 40% compare to 1:1 imaging beam optics. The usage of small imaging factors can help to maximize transmission for different gantry lattices, thus reducing treatment times

The impact of heart irradiation on dose-volume effects in the rat lung

Purpose: To test the hypothesis that heart irradiation increases the risk of a symptomatic radiation-induced loss of lung function (SRILF) and that this can be well-described as a modulation of the functional reserve of the lung. Methods and Materials: Rats were irradiated with 150-MeV protons. Dose-response curves were obtained for a significant increase in breathing frequency after irradiation of 100%, 75%, 50%, or 25% of the total lung volume, either including or excluding the heart from the irradiation field. A significant increase in the mean respiratory rate after 6-12 weeks compared with 0-4 weeks was defined as SRILF, based on biweekly measurements of the respiratory rate. The critical volume (CV) model was used to describe the risk of SRILF. Fits were done using a maximum likelihood method. Consistency between model and data was tested using a previously developed goodness-of-fit test. Results: The CV model could be fitted consistently to the data for lung irradiation only. However, this fitted model failed to predict the data that also included heart irradiation. Even refitting the model to all data resulted in a significant difference between model and data. These results imply that, although the CV model describes the risk of SRILF when the heart is spared, the model needs to be modified to account for the impact of dose to the heart on the risk of SRILE Finally, a modified CV model is described that is consistent to all data. Conclusions: The detrimental effect of dose to the heart on the incidence of SRILF can be described by a dose dependent decrease in functional reserve of the lung. (c) 2007 Elsevier Inc