The “Best-in-Physics” presentations are always a highlight of the AAPM Annual Meeting. With this year’s event once again a fully virtual experience, the traditional crowded poster session was replaced by a series of online talks showcasing the 15 top scoring abstracts. Here is part one of my selection from this year’s award winning studies. Keep an eye out for a second report appearing soon.
Dose-optimized MLC tracking deals with multi-target motion
Patients receiving radiotherapy for advanced cancers often have multiple tumour targets that require simultaneous irradiation. Each target, however, can exhibit large, independent motion. Emily Hewson from the University of Sydney’s ACRF Image X Institute described a new method for tracking multiple targets, using multileaf collimator (MLC) apertures optimized according to the accumulated 3D dose.
The Image X Institute team previously developed a real-time tracking method in which MLC apertures are adapted to individual target motion by shifting the aperture shape for each target to match its new position. They successfully applied this geometric-based approach to perform independent motion adaptation in real time on both an MRI-Linac and a standard linac.
However, the finite speed and leaf width of an MLC can cause dosimetric errors to accumulate during the treatment. “Geometric-based tracking has also been seen to be insufficient for multi-target tracking,” Hewson explained. “Complications from adapting the aperture to each individual target separately can result in dosimetric errors where the two targets overlap with each other.”
To improve motion tracking for multiple targets, the team developed an MLC tracking method that optimizes the adapted apertures based on the delivered dose – the most meaningful metric for radiotherapy. The technique works by calculating the accumulated 3D dose to the targets during treatment. If a target moves, the MLC apertures are adapted to minimize the difference between the planned and delivered doses accumulated up to that point. The dose delivered with the adapted aperture is then updated in real time.
To evaluate this approach, the researchers simulated radiation treatments of locally advanced prostate cancer using three methods: dose-optimized multi-target tracking; geometric-based tracking and no motion tracking. They simulated treatment plans for three prostate cancer patients and three different motion traces, and calculated the gamma failure rates for each method for the moving prostate and static lymph nodes.
“Dose-optimized tracking successfully reduced the failure rates compared to when no tracking was used for both targets,” said Hewson. “While geometric-based tracking did perform better than no tracking, dose-optimization was able to improve upon geometric-based tracking.” She noted that the dose-optimized tracking consistently showed the lowest errors for all three motion traces.
Examining the delivered dose distributions for the different plans revealed that geometric-based tracking caused overdosing to the regions where targets overlap. This error was eliminated with the dose-optimized tracking.
Hewson concluded that the dose-optimized tracking could improve upon the previous MLC tracking method for multi-target treatments. “Future work will look at integrating this method with a more advanced dose calculation algorithm. We will also include features such as further penalizing overdose to heathy tissue,” she said.
Radio-immunotherapy dose-painting boosts survival
In patients undergoing radiotherapy, the abscopal effect can lead to regression of tumours outside the radiation field, such as distant lesions or metastases. However, for “immunologically cold” tumours, such as castration-resistant prostate cancer, for example, such abscopal responses are rare. In an attempt to boost the abscopal effect, researchers at Harvard Medical School are investigating an approach known as radio-immunotherapy dose painting, or RAID.
Sayeda Yasmin-Karim described a series of investigations to assess this innovative approach using the SARRP small-animal radiation research platform. In one study, the team implanted mice with prostate cancer tumours on both flanks, irradiating one tumour and observing the other for signs of the abscopal effect. In some animals, the irradiated tumour was also treated with immunogenic biomaterial (IBM) loaded with anti-CD40 antibodies.
“We demonstrated that 5 Gy radiation to one of the tumours with intra-tumoural implantation of IBM to the same tumour caused the highest response to radiation for the treated, as well as the abscopal side,” Yasmin-Karim explained.
The researchers also irradiated a subvolume of the primary tumour and compared the outcome with irradiation of the full planning target volume. Sub-volume irradiation significantly reduced radiation damage to surrounding tissue, without impacting the tumour regression. Mice receiving the subvolume treatment also exhibited far longer survival.
Best in physics: clinical prompt gamma measurements and FLASH dosimetry
Having demonstrated that the RAID technique can substantially boost the abscopal response, Yasmin-Karim and colleagues next examined whether adding checkpoint inhibitors (anti-PD1 and anti-CTLA4) to activate the animals’ immune response could further enhance the abscopal effect. They observed a significant increase in survival in the cohort receiving IBM plus checkpoint inhibitors, particularly anti-PD1, where some mice survived for more than 250 days, compared with less than 50 days for the other treatment combinations.
“We have shown that radiotherapy plus IBM can significantly reduce castration-resistant prostate cancer growth, with radiation to the subvolume of the PTV or adding anti-PD1 further enhancing survival duration,” Yasmin-Karim concluded.
