Linear energy transfer incorporated intensity modulated proton therapy optimization

Cao, Wenhua; Khabazian, Azin; Yepes, P.; Lim, Gino J.; Poenisch, Falk; Grosshans, David R.; Mohan, Radhe

doi:10.1088/1361-6560/aa9a2e

Cited by 70 publications

(104 citation statements)

References 31 publications

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“…Cao et al have developed a method to simultaneously optimize the dose and LET d distributions of IMPT plans. Compared with the conventional IMPT plans, the plans generated using this LET d optimization strategy have elevated LET d in the target tumors and reduced LET d in the critical structures while maintaining the uniform physical dose distribution in the target tumors 36 .…”

mentioning

confidence: 99%

Exploring the advantages of intensity-modulated proton therapy: experimental validation of biological effects using two different beam intensity-modulation patterns

Ma¹,

Bronk²,

Kerr³

et al. 2020

Sci Rep

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in current treatment plans of intensity-modulated proton therapy, high-energy beams are usually assigned larger weights than low-energy beams. Using this form of beam delivery strategy cannot effectively use the biological advantages of low-energy and high-linear energy transfer (LET) protons present within the Bragg peak. However, the planning optimizer can be adjusted to alter the intensity of each beamlet, thus maintaining an identical target dose while increasing the weights of low-energy beams to elevate the Let therein. the objective of this study was to experimentally validate the enhanced biological effects using a novel beam delivery strategy with elevated LET. We used Monte Carlo and optimization algorithms to generate two different intensity-modulation patterns, namely to form a downslope and a flat dose field in the target. We spatially mapped the biological effects using high-content automated assays by employing an upgraded biophysical system with improved accuracy and precision of collected data. In vitro results in cancer cells show that using two opposed downslope fields results in a more biologically effective dose, which may have the clinical potential to increase the therapeutic index of proton therapy.Worldwide the number of proton therapy centers has increased dramatically in recent years 1 . The expansion of proton therapy centers can be attributed to multiple factors. The first and foremost advantage of protons is that a Bragg-peak dose profile appears at the end of the range of a proton beam. The use of different beam modulation and shaping techniques makes it possible to deliver a uniform high dose to the tumors while sparing the surrounding normal tissues 2 . The uniform target dose can be achieved using the passive-scattering proton therapy (PSPT) technique or the more advanced intensity-modulated proton therapy (IMPT) technique employing scanned beams. Importantly, some clinical trials have indicated the advantages of proton therapy over traditional photon-based therapy 3-6 . However, there are still many challenging issues in modern proton therapy. One of the them is that the radiobiological characteristics of proton therapy have yet to be completely understood. In current clinical practice, the relative biological effectiveness (RBE) of protons to reference photons, such as x-rays from a

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confidence: 99%

Exploring the advantages of intensity-modulated proton therapy: experimental validation of biological effects using two different beam intensity-modulation patterns

Ma¹,

Bronk²,

Kerr³

et al. 2020

Sci Rep

Self Cite

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show abstract

“…Besides, a recent study in prostate cancer has found that it is not possible to simultaneously meet the tumor and rectal constrains for both physical and variable RBE‐weighted dose, the latter being estimated based on in vitro cell survival data. In fact, other groups have decided to avoid the sometimes controversial concept of proton RBE completely and have tackled this problem by performing the optimization directly on LET distributions or proposing new beam orientations or treatment modalities …”

Section: Introductionmentioning

confidence: 99%

“…Besides, a recent study in prostate cancer 34 has found that it is not possible to simultaneously meet the tumor and rectal constrains for both physical and variable RBEweighted dose, the latter being estimated based on in vitro cell survival data. In fact, other groups have decided to avoid the sometimes controversial concept of proton RBE completely and have tackled this problem by performing the optimization directly on LET distributions [35][36][37][38][39] or proposing new beam orientations or treatment modalities. [40][41][42] Our proposed solution is the use of a mixed RBE model (MultiRBE) for plan optimization, where a uniform RBE is used in the target contours to ensure an adequate tumor coverage in terms of physical dose, but a variable RBE is used elsewhere.…”

Section: Introductionmentioning

confidence: 99%

MultiRBE: Treatment planning for protons with selective radiobiological effectiveness

Sánchez-Parcerisa

López-Aguirre

Llerena³

et al. 2019

Medical Physics

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Purpose Clinical treatment planning protocols for protons recommend a uniform value radiobiological effectiveness (RBE) of protons of 1.1 throughout the treatment field, despite evidence from in‐vitro and animal studies that proton RBE increases with linear energy transfer (LET), causing tissues placed distally to the target location to receive a presumably higher biological dose than estimated. While several voices in the medical physics community have advocated for variable RBE‐based optimization, the uncertainties in RBE models have prevented its implementation in clinical practice, since an overestimation of RBE could cause significant target underdosage. Methods We propose a mixed RBE model (MultiRBE), where a uniform RBE is used in the target contours to ensure an adequate tumor coverage in terms of physical dose, but a variable RBE is used elsewhere. Our model was implemented in the open‐source treatment planning system matRad and three example cases were planned: a homogeneous phantom, a prostate tumor and a head‐and‐neck case. MultiRBE was used for plan optimization, and the produced plans were subsequently evaluated in terms of physical dose coverage (V95%) and variable RBE‐weighted dose in organs at risk and normal tissue complication probabilities (NTCP), where prediction models were available. Results The planning algorithm showed potential for reducing the biological dose in organs surrounding the planning target and thus decreasing the probability for complications in normal tissue (by up to 62% in the prostate case and 37% in the head‐and‐neck patient). This was achieved without compromising the target coverage or homogeneity in terms of physical dose, as a result of a smarter redistribution of dose among the surrounding tissues with regard to the optimization constraints. Conclusions The results prove the ability of the MultiRBE model to reduce biological dose at healthy tissues without compromising the dose coverage of the tumor, with independence of the variable RBE models used.

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“…Adding explicit terms in consideration of the LET distribution to the objective function of IMPT enables the control of the LET distribution, for example, by suppressing LET to OARs and/or concentrating LET on tumors. In fact, different versions of LET optimization techniques in this regard have been proposed by several groups, and recently, techniques have been developed to specifically incorporate the optimization of the LET d distribution into robust optimization . Using these techniques, it should become possible to further reduce the deviation not only for the OARs close to the tumor but also for the OARs distant from the tumor.…”

Section: Discussionmentioning

confidence: 99%

Difference in LET‐based biological doses between IMPT optimization techniques: Robust and PTV‐based optimizations

Hirayama

Matsuura

Yasuda

et al. 2020

J Applied Clin Med Phys

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Purpose: While a large amount of experimental data suggest that the proton relative biological effectiveness (RBE) varies with both physical and biological parameters, current commercial treatment planning systems (TPS) use the constant RBE instead of variable RBE models, neglecting the dependence of RBE on the linear energy transfer (LET). To conduct as accurate a clinical evaluation as possible in this circumstance, it is desirable that the dosimetric parameters derived by TPS (D RBE¼1:1 ) are close to the "true" values derived with the variable RBE models (D vRBE ). As such, in this study, the closeness of D RBE¼1:1 to D vRBE was compared between planning target volume (PTV)-based and robust plans.Methods: Intensity-modulated proton therapy (IMPT) treatment plans for two Radiation Therapy Oncology Group (RTOG) phantom cases and four nasopharyngeal cases were created using the PTV-based and robust optimizations, under the assumption of a constant RBE of 1.1. First, the physical dose and dose-averaged LET (LET d ) distributions were obtained using the analytical calculation method, based on the pencil beam algorithm. Next, D vRBE was calculated using three different RBE models. The deviation of D vRBE from D RBE¼1:1 was evaluated with D 99 and D max , which have been used as the evaluation indices for clinical target volume (CTV) and organs at risk (OARs), respectively. The influence of the distance between the OAR and CTV on the results was also investigated. As a measure of distance, the closest distance and the overlapped volume histogram were used for the RTOG phantom and nasopharyngeal cases, respectively.Results: As for the OAR, the deviations of D vRBE max from D RBE¼1:1 max were always smaller in robust plans than in PTV-based plans in all RBE models. The deviation would tend to increase as the OAR was located closer to the CTV in both optimization techniques. As for the CTV, the deviations of D vRBE 99 from D RBE¼1:1 99 were comparable between the two optimization techniques, regardless of the distance between the CTV and the OAR.---

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Linear energy transfer incorporated intensity modulated proton therapy optimization

Cited by 70 publications

References 31 publications

Exploring the advantages of intensity-modulated proton therapy: experimental validation of biological effects using two different beam intensity-modulation patterns

Exploring the advantages of intensity-modulated proton therapy: experimental validation of biological effects using two different beam intensity-modulation patterns

MultiRBE: Treatment planning for protons with selective radiobiological effectiveness

Difference in LET‐based biological doses between IMPT optimization techniques: Robust and PTV‐based optimizations

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