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Particle therapy

Particle therapy

How does respiratory motion impact pencil-beam scanning proton therapy?

06 Apr 2020
Measurement set-up

Intensity-modulated proton therapy (IMPT) delivered via proton pencil-beam scanning (PBS) is one of the most precise methods available to target tumours with high radiation doses while minimizing the impact to surrounding healthy tissue. However, the interplay effect, caused by interaction of respiratory-related tumour motion and the motion of the proton beam, can negatively affect radiation dose distribution.

Much research has been published about the interplay effect. A measurement-based study of symmetric and asymmetric breathing patterns from the University of Cincinnati College of Medicine has now reconfirmed that standard fractionation can be used to treat moving targets with symmetric motion amplitude less than 5 mm, and that using a higher fractionation regimen will help minimize interplay effect-caused degradation of target dose. But the study also found that this is not the case for small tumour targets affected by large motion and irregular breathing patterns  (J. Appl. Clin. Med. Phys. 10.1002/acm2.12846).

By measuring beam delivery of up to 15 treatment fractions, with different symmetric and asymmetric breathing patterns, the researchers determined that irregular motion causes systematic errors that cannot be recovered by increasing fractionation. For patients with irregular breathing, patient-specific motion management is needed to ensure effective dose delivery to the target tumour and to reduce toxicities to surrounding healthy tissue.

Principal investigator Eunsin Lee and colleagues quantified the dosimetric influence of the interplay effect for different target sizes, motion amplitudes and pencil-beam spot sizes. They did not use any simulation models or treatment delivery logfiles, but rather delivered an actual fractional dose of 200 cGy multiple times for a specific number of fractions.

Eunsin Lee

“In PBS proton therapy, each layer is delivered in a series of discrete pencil beam spots. The scanning magnets are used to reconfigure the system to deliver dose in the subsequent position,” explains Lee. “This is not an instantaneous process. In the presence of tumour motion due to respiration, the spot can be delivered in an incorrect position. This makes scanning proton beams inherently sensitive to motion, because in addition to the motion of the tumour, the beam itself is also moving during the delivery.”

“The effect is random, so if a desired dose is delivered in a small fractional dose in multiple days, the interplay effects can be mitigated,” he adds. “We wanted to quantify how differently fractionation mitigates the interplay effect by utilizing a conformity index and a homogeneity index and as a function of fractionations.”

The team generated treatment plans to mimic 3- and 10-cm diameter spherical targets, at 1 and 5 cm depths in a solid water phantom. All target volumes were covered by 95% isodose line. They simulated respiratory motion ranges of ±0.5, ±1.0 and ± 2.0 cm, using sine and cosine4 waves to represent sinusoidal symmetric and realistic asymmetric breathing patterns, respectively.

The researchers delivered a dose of 200 cGy per fraction in 1, 5, 10 and 15 fractions. For the small 3 cm target, they used an energy spectrum of eight layers with 119 spots at the shallow depth, and nine layers with 296 spots at the deeper depth. For the larger 10 cm targets, they used 22 layers with 1488 spots at 1 cm and 23 layers with 4615 spots at 5 cm.

They then evaluated the dose conformity and uniformity of each measurement dataset at the centre plane of each moving target. They determined that breathing patterns had a larger impact on dose distribution conformity, but less impact on homogeneity. Dose homogeneity was impacted to a greater extent by intrinsic beam spot characteristics.

Based on their actual measurements, the researchers reconfirmed findings of prior studies that the interplay effect decreased as the numbers of fractions delivered increased. However, increasing fractionation did not improve dose conformity or homogeneity in cases of relatively large motion, such as deep breathing by a patient when a small tumour was being targeted.

“Our study was limited to investigating PBS interplay effect with a simple geometric shape of a moving target in a homogeneous water phantom and evaluating the motion-affected dose in 2D plane measurements,” says Lee. “We recognize that the interplay effect on PBS delivery with irregular target geometry, under realistic patient-specific breathing motion and with the high heterogeneity of a real patient body may be much more complicated to quantify.”

Next, the team plans to investigate interplay effects on several real patient cases using anthropomorphic phantom studies such as breast, lung and liver that require motion management techniques such as respiratory gating and breath hold.

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