Adaptive radiotherapy, an advanced cancer treatment in which each fraction is tailored to the patient’s daily anatomy, offers the potential to maximize target conformality and minimize dose to surrounding healthy tissue. Based on daily scans – such as MR images recorded by an MR-Linac, for example – treatment plans are adjusted each day to account for anatomical changes in the tumour and surrounding healthy tissue.

Creating a new plan for every treatment fraction, however, increase the potential for errors, making fast and effective quality assurance (QA) procedures more important than ever. To meet this need, the physics team at Hospital Almater in Mexicali, Mexico, is using Elekta ONE | QA, powered by ThinkQA Secondary Dose Check^* (ThinkQA SDC) software to ensure that each adaptive plan is safe and accurate before it is delivered to the patient.

Radiotherapy requires a series of QA checks prior to treatment delivery, starting with patient-specific QA, where the dose calculated by the treatment planning system is delivered to a phantom. This procedure ensures that the delivered dose distribution matches the prescribed plan. Alongside, secondary dose checks can be performed, in which an independent algorithm verifies that the calculated dose distribution corresponds with that delivered to the actual patient anatomy.

“The secondary dose check is an independent dose calculation that uses a different algorithm to the one in the treatment planning system,” explains Alexis Cabrera Santiago, a medical physicist at Hospital Almater. “ThinkQA SDC software calculates the dose based on the patient anatomy, which is actually more realistic than using a rigid phantom, so we can compare both results and catch any differences before treatment.”

For adaptive radiotherapy in particular, this second check is invaluable. Performing phantom-based QA following each daily imaging session is often impractical. Instead, in many cases, it’s possible to use ThinkQA SDC instead.

“Secondary dose calculation is necessary in adaptive treatments, for example using the MR-Linac, because you are changing the treatment plan for each session,” says José Alejandro Rojas‑López, who commissioned and validated ThinkQA SDC at Hospital Almater. “You are not able to shift the patient to realise patient-specific QA, so this secondary dose check is needed to analyse each treatment session.”

ThinkQA SDC’s ability to achieve patient-specific QA without shifting the patient is extremely valuable, allowing time savings while upholding the highest level of QA safety. “The AAPM TG 219 report recognises secondary dose verification as a validated alternative to patient-specific QA, especially when there is no time for traditional phantom checks in adaptive fractions,” adds Cabrera Santiago.

The optimal choice

At Hospital Almater, all external-beam radiation treatments are performed using an Elekta Unity MR-Linac (with brachytherapy employed for gynaecological cancers). This enables the hospital to offer adaptive radiotherapy for all cases, including head-and-neck, breast, prostate, rectal and lung cancers.

To ensure efficient workflow and high-quality treatments, the team turned to the ThinkQA SDC software. ThinkQA SDC received FDA 510(k) clearance in early 2024 for use with both the Unity MR-Linac and conventional Elekta linacs.

Rojas‑López (who now works at Hospital Angeles Puebla) says that the team chose ThinkQA SDC because of its user-friendly interface, ease of integration into the clinical workflow and common integrated QA platform for both CT and MR-Linac systems. The software also offers the ability to perform 3D evaluation of the entire planning treatment volume (PTV) and the organs-at-risk, making the gamma evaluation more robust.

Commissioning of ThinkQA SDC was fast and straightforward, Rojas‑López notes, requiring minimal data input into the software. For absolute dose calibration, the only data needed are the cryostat dose attenuation response, the output dose geometry and the CT calibration.

“This makes a difference compared with other commercial solutions where you have to introduce more information, such as MLC [multileaf collimator] leakage and MLC dosimetric leaf gap, for example,” he explains. “If you have to introduce more data for commissioning, this delays the clinical introduction of the software.”

Cabrera Santiago is now using ThinkQA SDC to provide secondary dose calculations for all radiotherapy treatments at Hospital Almater. The team has established a protocol with a 3%/2 mm gamma criterion, a tolerance limit of 95% and an action limit of 90%. He emphasizes that the software has proved robust and flexible, and provides confidence in the delivered treatment.

“ThinkQA SDC lets us work with more confidence, reduces risk and saves time without losing control over the patient’s safety,” he says. “It checks that the plan is correct, catches issues before treatment and helps us find any problems like set-up errors, contouring mistakes and planning issues.”

The software integrates smoothly into the Elekta ONE adaptive workflow, providing reliable results without slowing down the clinical workflow. “In our institution, we set up ThinkQA SDC so that it automatically receives the new plan, runs the check, compares it with the original plan and creates a report – all in around two minutes,” says Cabrera Santiago. “This saves us a lot of time and removes the need to do everything manually.”

A case in point

As an example of ThinkQA SDC’s power to ease the treatment workflow, Rojas‑López describes a paediatric brain tumour case at Hospital Almater. The young patient needed sedation during their treatment, requiring the physics team to optimize the treatment time for the entire adaptive radiotherapy workflow. “ThinkQA SDC served to analyse, in a fast mode, the treatment plan QA for each session. The measurements were reliable, enabling us to deliver all of the treatment sessions without any delay,” he explains.

Indeed, the ability to use secondary dose checks for each treatment fraction provides time advantages for the entire clinical workflow over phantom-based pre-treatment QA. “Time in the bunker is very expensive,” Rojas‑López points out. “If you reduce the time required for QA, you can use the bunker for patient treatments instead and treat more patients during the clinical time. Secondary dose check can optimize the workflow in the entire department.”

Importantly, in a recent study comparing patient-specific QA measurements using Sun Nuclear’s ArcCheck with ThinkQA SDC calculations, Rojas‑López and colleagues confirmed that the two techniques provided comparable results, with very similar gamma passing rates. As such, they are working to reduce phantom measurements and, in most cases, replace them with a secondary dose check using ThinkQA SDC.

The team at Hospital Almater concur that ThinkQA SDC provides a reliable tool to evaluate radiation treatments, including the first fraction and all of the adaptive sessions, says Rojas‑López. “You can use it for all anatomical sites, with reliable and confident results,” he notes. “And you can reduce the need for measurements using another patient-specific QA tool.”

“I think that any centre doing adaptive radiotherapy should seriously consider using a tool like ThinkQA SDC,” adds Cabrera Santiago.

*ThinkQA is manufactured by DOSIsoft S.A. and distributed by Elekta.

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Researchers at the University of Victoria in Canada are developing a low-cost radiotherapy system for use in low- and middle-income countries and geographically remote rural regions. Initial performance characterization of the proof-of-concept device produced encouraging results, and the design team is now refining the system with the goal of clinical commercialization.

This could be good news for people living in low-resource settings, where access to cancer treatment is an urgent global health concern. The WHO’s International Agency for Research on Cancer estimates that there are at least 20 million new cases of cancer diagnosed annually and 9.7 million annual cancer-related deaths, based on 2022 data. By 2030, approximately 75% of cancer deaths are expected to occur in low- and middle-income countries, due to rising populations, healthcare and financial disparities, and a general lack of personnel and equipment resources compared with high-income countries.

The team’s orthovoltage radiotherapy system, known as KOALA (kilovoltage optimized alternative for adaptive therapy), is designed to create, optimize and deliver radiation treatments in a single session. The device, described in Biomedical Physics & Engineering Express, consists of a dual-robot system with a 225 kVp X-ray tube mounted onto one robotic arm and a flat-panel detector mounted on the other.

The same X-ray tube can be used to acquire cone-beam CT (CBCT) images, as well as to deliver treatment, with a peak tube voltage of 225 kVp and a maximum tube current of 2.65 mA for a 1.2 mm focal spot. Due to its maximum reach of 2.05 m and collision restrictions, the KOALA system has a limited range of motion, achieving 190° arcs for both CBCT acquisition and treatments.

Device testing

To characterize the KOALA system, lead author Olivia Masella and colleagues measured X-ray spectra for tube voltages of 120, 180 and 225 kVp. At 120 and 180 kVp, they observed good agreement with spectra from SpekPy (a Python software toolkit for modelling X-ray tube spectra). For the 225 kVp spectrum, they found a notable overestimation in the higher energies.

The researchers performed dosimetric tests by measuring percent depth dose (PDD) curves for a 120 kVp imaging beam and a 225 kVp therapy beam, using solid water phantom blocks with a Farmer ionization chamber at various depths. They used an open beam with 40° divergence and a source-to-surface distance of 30 cm. They also measured 2D dose profiles with radiochromic film at various depths in the phantom for a collimated 225 kVp therapy beam and a dose of approximately 175 mGy at the surface.

The PDD curves showed excellent agreement between experiment and simulations at both 120 and 225 kVp, with dose errors of less than 2%. The 2D profile results were less than optimal. The team aims to correct this by using a more optimal source-to-collimator distance (100 mm) and a custom-built motorized collimator.

Geometrical evaluation conducted using a coplanar star-shot test showed that the system demonstrated excellent geometrical accuracy, generating a wobble circle with a diameter of just 0.3 mm.

Low costs and clinical practicality

Principal investigator Magdalena Bazalova-Carter describes the rationale behind the KOALA’s development. “I began the computer simulations of this project about 15 years ago, but the idea originated from Michael Weil, a radiation oncologist in Northern California,” she tells Physics World. “He and our industrial partner, Tai-Nang Huang, the president of Linden Technologies, are overseeing the progress of the project. Our university team is diversified, working in medical physics, computer science, and electrical and mechanical engineering. Orimtech, a medical device manufacturer and collaborator, developed the CBCT acquisition and reconstruction software and built the imaging prototype.”

Masella says that the team is keeping costs low is various ways. “Megavoltage X-rays are most commonly used in conventional radiotherapy, but KOALA’s design utilizes low-energy kilovoltage X-rays for treatment. By using a 225 kVp X-ray tube, the X-ray generation alone is significantly cheaper compared to a conventional linac, at a cost of USD $150,000 compared to $3 million,” she explains. “By operating in the kilovoltage instead of megavoltage range, only about 4 mm of lead shielding is required, instead of 6 to 7 feet of high-density concrete, bringing the shielding cost down from $2 million to $50,000. We also have incorporated components that are much lower cost than [those in] a conventional radiotherapy system.”

“Our novel iris collimator leaves are only 1-mm thick due to the lower treatment X-ray beam energy, and its 12 leaves are driven by a single motor,” adds Bazalova-Carter. “Although multileaf collimators with 120 leaves utilized with megavoltage X-ray radiotherapy are able to create complex fields, they are about 8-cm thick and are controlled by 120 separate motors. Given the high cost and mechanical vulnerability of multileaf collimators, our single motor design offers a more robust and reliable alternative.”

The team is currently developing a new motorized collimator, an improved treatment couch and a treatment planning system. They plan to improve CBCT imaging quality with hardware modifications, develop a CBCT-to-synthetic CT machine learning algorithm, refine the auto-contouring tool and integrate all of the software to smooth the workflow.

The researchers are planning to work with veterinarians to test the KOALA system with dogs diagnosed with cancer. They will also develop quality assurance protocols specific to the KOALA device using a dog-head phantom.

“We hope to demonstrate the capabilities of our system by treating beloved pets for whom available cancer treatment might be cost-prohibitive. And while our system could become clinically adopted in veterinary medicine, our hope is that it will be used to treat people in regions where conventional radiotherapy treatment is insufficient to meet demand,” they say.

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Electron therapy has long played an important role in cancer treatments. Electrons with energies of up to 20 MeV can treat superficial tumours while minimizing delivered dose to underlying tissues; they are also ideal for performing total skin therapy and intraoperative radiotherapy. The limited penetration depth of such low-energy electrons, however, limits the range of tumour sites that they can treat. And as photon-based radiotherapy technology continues to progress, electron therapy has somewhat fallen out of fashion.

That could all be about to change with the introduction of radiation treatments based on very high-energy electrons (VHEEs). Once realised in the clinic, VHEEs – with energies from 50 up to 400 MeV – will deliver highly penetrating, easily steerable, conformal treatment beams with the potential to enable emerging techniques such as FLASH radiotherapy. French medical technology company THERYQ is working to make this opportunity a reality.

Therapeutic electron beams are produced using radio frequency (RF) energy to accelerate electrons within a vacuum cavity. An accelerator of a just over 1 m in length can boost electrons to energies of about 25 MeV – corresponding to a tissue penetration depth of a few centimetres. It’s possible to create higher energy beams by simply daisy chaining additional vacuum chambers. But such systems soon become too large and impractical for clinical use.

THERYQ is focusing on a totally different approach to generating VHEE beams. “In an ideal case, these accelerators allow you to reach energy transfers of around 100 MeV/m,” explains THERYQ’s Sébastien Curtoni. “The challenge is to create a system that’s as compact as possible, closer to the footprint and cost of current radiotherapy machines.”

Working in collaboration with CERN, THERYQ is aiming to modify CERN’s Compact Linear Collider technology for clinical applications. “We are adapting the CERN technology, which was initially produced for particle physics experiments, to radiotherapy,” says Curtoni. “There are definitely things in this design that are very useful for us and other things that are difficult. At the moment, this is still in the design and conception phase; we are not there yet.”

VHEE advantages

The higher energy of VHEE beams provides sufficient penetration to treat deep tumours, with the dose peak region extending up to 20–30 cm in depth for parallel (non-divergent) beams using energy levels of 100–150 MeV (for field sizes of 10 x 10 cm or above). And in contrast to low-energy electrons, which have significant lateral spread, VHEE beams have extremely narrow penumbra with sharp beam edges that help to create highly conformal dose distributions.

“Electrons are extremely light particles and propagate through matter in very straight lines at very high energies,” Curtoni explains. “If you control the initial direction of the beam, you know that the patient will receive a very steep and well defined dose distribution and that, even for depths above 20 cm, the beam will remain sharp and not spread laterally.”

Electrons are also relatively insensitive to tissue inhomogeneities, such as those encountered as the treatment beam passes through different layers of muscle, bone, fat or air. “VHEEs have greater robustness against density variations and anatomical changes,” adds THERYQ’s Costanza Panaino. “This is a big advantage for treatments in locations where there is movement, such as the lung and pelvic areas.”

It’s also possible to manipulate VHEEs via electromagnetic scanning. Electrons have a charge-to-mass ratio roughly 1800 times higher than that of protons, meaning that they can be steered with a much weaker magnetic field than required for protons. “As a result, the technology that you are building has a smaller footprint and the possibility costing less,” Panaino explains. “This is extremely important because the cost of building a proton therapy facility is prohibitive for some countries.”

Enabling FLASH

In addition to expanding the range of clinical indications that can be treated with electrons, VHEE beams can also provide a tool to enable the emerging – and potentially game changing – technique known as FLASH radiotherapy. By delivering therapeutic radiation at ultrahigh dose rates (higher than 100 Gy/s), FLASH vastly reduces normal tissue toxicity while maintaining anti-tumour activity, potentially minimizing harmful side-effects.

The recent interest in the FLASH effect began back in 2014 with the report of a differential response between normal and tumour tissue in mice exposed to high dose-rate, low-energy electrons. Since then, most preclinical FLASH studies have used electron beams, as did the first patient treatment in 2019 – a skin cancer treatment at Lausanne University Hospital (CHUV) in Switzerland, performed with the Oriatron eRT6 prototype from PMB-Alcen, the French company from which THERYQ originated.

FLASH radiotherapy is currently being used in clinical trials with proton beams, as well as with low-energy electrons, where it remains intrinsically limited to superficial treatments. Treating deep-seated tumours with FLASH requires more highly penetrating beams. And while the most obvious option would be to use photons, it’s extremely difficult to produce an X-ray beam with a high enough dose rate to induce the FLASH effect without excessive heat generation destroying the conversion target.

“It’s easier to produce a high dose-rate electron beam for FLASH than trying to [perform FLASH] with X-rays, as you use the electron beam directly to treat the patient,” Curtoni explains. “The possibility to treat deep-seated tumours with high-energy electron beams compensates for the fact that you can’t use X-rays.”

Panaino points out that in addition to high dose rates, FLASH radiotherapy also relies on various interdependent parameters. “Ideally, to induce the FLASH effect, the beam should be pulsed at a frequency of about 100 Hz, the dose-per-pulse should be 1 Gy or above, and the dose rate within the pulse should be higher than 10⁶ Gy/s,” she explains.

Into the clinic

THERYQ is using its VHEE expertise to develop a clinical FLASH radiotherapy system called FLASHDEEP, which will use electrons at energies of 100 to 200 MeV to treat tumours at depths of up to 20 cm. The first FLASHDEEP systems will be installed at CHUV (which is part of a consortium with CERN and THERYQ) and at the Gustave Roussy cancer centre in France.

“We are trying to introduce FLASH into the clinic, so we have a prototype FLASHKNiFE machine that allows us to perform low-energy, 6 and 9 MeV, electron therapy,” says Charlotte Robert, head of the medical physics department research group at Gustave Roussy. “The first clinical trials using low-energy electrons are all on skin tumours, aiming to show that we can safely decrease the number of treatment sessions.”

While these initial studies are limited to skin lesions, clinical implementation of the FLASHDEEP system will extend the benefits of FLASH to many more tumour sites. Robert predicts that VHEE-based FLASH will prove most valuable for treating radioresistant cancers that cannot currently be cured. The rationale is that FLASH’s ability to spare normal tissue will allow delivery of higher target doses without increasing toxicity.

“You will not use this technology for diseases that can already be cured, at least initially,” she explains. “The first clinical trial, I’m quite sure, will be either glioblastoma or pancreatic cancers that are not effectively controlled today. If we can show that VHEE FLASH can spare normal tissue more than conventional radiotherapy can, we hope this will have a positive impact on lesion response.”

“There are a lot of technological challenges around this technology and we are trying to tackle them all,” Curtoni concludes. “The ultimate goal is to produce a VHEE accelerator with a very compact beamline that makes this technology and FLASH a reality for a clinical environment.”

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