Aiming for the bull’s eye with ADAPTNOW.
With the Holland Particle Therapy Centre opening its doors in 2017, proton therapy will soon be available in the Netherlands. This novel therapy promises high-precision cancer treatment.
The technique is very sensitive to daily variations in the patient’s anatomy. “For instance, a change in rectum filling may cause the proton beams to partly miss the tumour if no counter-measures are taken,” says Dr Mischa Hoogeman of Erasmus MC. Together with Dennis Schaart of TU Delft and Marius Staring of LUMC, he is developing methods to target tumours more precisely.
Hoogeman is Research Coordinator at the Holland Particle Therapy Centre (HollandPTC), which is the forthcoming proton therapy institute of Medical Delta partners Erasmus MC, LUMC and TU Delft. “In radiotherapy, the radiation’s energy damages the DNA of cancer cells, causing them to die or stop growing,” explains Hoogeman. “Traditional radiotherapy employs X-ray beams, which deposit a gradually decreasing dose of radiation along the ray’s path through the patient. As a result, the healthy tissues around the tumour are irradiated with a non-negligible dose, causing side-effects.”
Intensity-modulated proton therapy (IMPT) employs protons, which have different physical properties. Their energy loss is small when they enter the body, then reaches a maximum point (known as the Bragg peak) at a specific depth, and then quickly decreases to zero. The protons can be directed into a narrow beam using strong magnets. A radiation technologist can precisely modulate the dose distribution and the location of the Bragg peak by adjusting the intensity, energy and direction of the proton beams. This is all incorporated in a personalised treatment plan for the patient. “IMPT has a unique potential to target the tumour and spare healthy tissue, making it especially suitable to treat tumours surrounded by radio-sensitive tissues,” says Hoogeman.
However, IMPT’s highly localised effect also makes it sensitive to daily variations in the patient’s anatomy. Radiotherapy may consist of 30 daily irradiation sessions, each lasting a few minutes. The treatment plan (i.e., intensities, energies, and directions of the proton beams) is made before the first session. This is a time-consuming job in which a radiation oncologist draws the tumour contours on a CT scan. The optimal proton beam properties are subsequently calculated. “It’s not feasible to repeat this procedure every day, because it may take several hours,” says Hoogeman.
The size and position of the tumour may change in the course of the treatment. For instance, in the case of prostate cancer, bladder and rectum filling may affect the tumour’s position. And the tumour may gradually shrink if the therapy is successful. This may cause a severe overdose to healthy tissues or an underdose to the tumour. At present, anatomical variations are accounted for in the treatment plan by irradiating surrounding healthy tissue. “So we’re not fully exploiting the superior physical properties of protons yet,” explains Hoogeman.
HollandPTC expects its first patient in late autumn 2017. It will treat approximately 600 patients a year. “It would be great if we could even better exploit the advantages of protons in the first years after opening,” says Dr Marius Staring of LUMC. “So Mischa, Dennis and I have started a Medical Delta research project ADAPTNOW, in which we’re developing software to automatically depict the patient’s internal anatomy and rapidly adapt the treatment plan before each irradiation session. In addition, we’re developing technologies to verify the dose delivery during the irradiation.”
“The equipment for these three steps will all be present in the HollandPTC treatment room: a CT scanner, proton therapy equipment, and instruments to determine the dose delivery,” says Staring. “If our project succeeds, a treatment session will consist of the following steps: the patient lies down on a treatment table and a CT scan is performed. A robot then carefully moves the table with the patient to the proton-delivery equipment within 30 seconds. Our software uses this short time window to calculate the tumour’s current size and position, and adjusts the irradiation plan accordingly. Anatomical changes within 30 seconds are usually negligible. The irradiation starts after a final verification of the patient’s alignment and the dose delivery is immediately monitored.”
Staring’s team at LUMC specialises in image processing. “We’ve developed algorithms that can automatically determine the tumour’s current contours by comparing the daily CT scan with the CT scan that was made before the first session,” he explains. “These algorithms are very accurate, but it is a challenge to make them faster than 30 seconds. We’re very close to achieving this speed now, which is fantastic.”
While the team in Leiden is developing the automatic contouring software, their collaborators in Rotterdam are focusing on the subsequent adaptation of the irradiation plan. “We’ve already developed algorithms to restore the dose distribution within a few minutes. Now, we’re working on methods to speed up the algorithms using the daily contours. Eventually, the automatic contouring step and the optimisation of the irradiation plan should both be performed within 30 seconds.”
The expertise of the three institutes is nicely complementary. Dr. ir. Dennis Schaart, TU Delft
Verifying the dose
Meanwhile, the team in Delft is working on an in vivo quality control step, verifying the delivered dose during the irradiation. “Given the complexity of the new methods,” says Dr. Dennis Schaart, “we want to be absolutely sure that the process will be as precise as possible. Ideally, we’d like to be able to monitor the dose distribution in the patient’s body during each irradiation session.”
The researchers have developed a clever method to make this possible. “When protons hit atomic nuclei in the body, so-called ‘prompt gamma photons’ are produced,” says Schaart. “These leave the body without causing any harm. Once the proton beams have delivered their full dose, they will stop producing prompt gamma photons. By detecting the gamma photons with special cameras, we can deduce the dose distribution. We can use this information as a safety check during the treatment and to adjust the irradiation plan of the next session if necessary. This method already works in a simple plastic body model, in which we can determine the target position with one-millimetre accuracy. The situation in a real patient is more complex, because a body consists of multiple tissue types with different properties. We’re now working on methods to properly analyse these complex real-life data.”
The three men have been collaborating for some time now and form a well-oiled team. “We clicked at once. The expertise of our three institutions is nicely complementary, so we can really offer each other something and we inspire each other. We are working hard to be able to implement our methods soon in HollandPTC,” says Schaart.
Interview by: Linda van den Berg
For more information on the project contact:
Dr. Mischa Hoogeman, Dr. ir. Dennis Schaart or Dr. ir. Marius Staring