The symposium began with an opening address from PMB's Editor-in-Chief Simon Cherry, from the University of California, Davis. Cherry took a look back at the very first issue of PMB, and shared some of the journal's most cited papers and most prolific authors. The podium was then turned over to five of PMB's current board members to examine the past, present and future of medical physics.

The medical physics revolution

Steven Meikle from the University of Sydney described just how far medical physics has come in the last 60 years. Looking first at the current state-of-the-art in cancer diagnostics, he explained how this involves anatomical imaging with CT, ultrasound or MRI, plus PET/CT scans for staging. Treatment planning can be based on CT, MRI or PET/CT, as can post-treatment imaging to monitor effectiveness. In 1956, only planar X-ray imaging was available. This was used for diagnosis, but not routinely for planning, while post-therapy monitoring relied solely on clinical observation.

For radiotherapy, treatment planning in 2016 uses model-based or Monte Carlo methods. Radiation is delivered via conformal techniques such as intensity-modulated radiotherapy (IMRT), image-guided radiotherapy (IGRT), volumetric-modulated arc therapy (VMAT) and stereotactic body radiotherapy (SBRT), using X-rays, electrons, photons or ions. Verification is performed after, or even during, treatment delivery. In 1956, plans were hand-calculated based on anatomical landmarks and delivered using kilovoltage X-rays or high-energy gamma rays.

"You can see by comparing workflows that imaging has made a huge contribution to the way we practise cancer diagnosis and staging, and medical physics has played a big part in that," explained Meikle. "Medical physics has also made a big contribution to the way external-beam radiotherapy is applied for cancer treatment."

Meikle examined the major advances that enabled this "medical-physics revolution". "In imaging, I nominate tomographic reconstruction as the single biggest advance that moved the field forward," he declared. Indeed, the significance of this development was recognized back in 1979, when Allan Cormack and Godfrey Hounsfield won the Nobel Prize in Physiology or Medicine for their development of computer-assisted tomography.

In radiotherapy, major advances concern the emergence of conformal radiotherapy, including beam shaping with multi-leaf collimators in the 1980s, IMRT in the 1990s and IGRT in the 2000s. "All of these progress radiotherapy treatment planning and delivery to allow much more conformal and precise dose distributions," he said.

Meikle concluded by considering how such advances impact patients. "Over the last 60 years, medical physics has helped to reduce cancer mortality and improve quality-of-life for cancer patients," he said. "Life expectancy is greater now than 60 years ago. But we are also losing more years to ill health and disability. It's easy to look back and think all the problems have been solved. But chronic illness is still a big problem – and medical physicists are well equipped to help solve this problem."

Evolutions in diagnostic imaging

Next to speak, Brian Pogue from Dartmouth discussed the evolution of diagnostic imaging over the last 60 years. He noted that between the 1990s and 2000s, PMB saw a jump in imaging publications per year, with citations in this field growing even faster.

Pogue shared some example successes in medical imaging, such as low-dose CT, which was advanced by the development of new detectors, statistical modelling algorithms, iterative reconstruction and patient-specific scans, as well as public awareness of the need for low-dose scans. PET/CT and SPECT/CT, meanwhile, evolved thanks to hardware developments, improvements in reconstruction and widespread adoption.

Another example is X-ray tomosynthesis for breast imaging, which was enabled by new detectors and sources, reconstruction algorithms, CAD algorithms and screening recommendations. Elsewhere, dual- and multi-energy CT are now widely adopted, with the field in an exponential growth phase.

Then there's 3D ultrasound, which has benefited from faster digitization and 3D reconstruction techniques. "This might look like a technical curiosity, but its impact has been profound in both neonatal and breast-cancer imaging," Pogue pointed out. Other success stories include MRI breast and prostate applications, surgical guidance and radiotherapy positioning technologies, near-infrared spectroscopy and robotic procedures.

Pogue also described the use of contrast agents to improve resolution, contrast and function assessment, citing growth in the use of ultrasound microbubble contrast as one example. "We can use contrast agents to push imaging to its ultimate extent, by using super-resolution methods with bubble localization to achieve micron-level spatial resolution across a centimetre of tissue," he added.

Finally, Pogue mentioned some fundamentally new physical-imaging techniques that use multiple electromagnetic or acoustic spectral bands to image tissue with combined information streams. These included magnetic particle imaging, an embryonic field in a rapid growth phase, as well as photoacoustic imaging, bioluminescence and Cerenkov imaging. "PMB has published some of the most important papers," he noted.

See what you treat

Bas Raaymakers from UMC Utrecht considered the need for image guidance during radiation therapy. With advanced modalities such as IMRT allowing the sculpting of dose distribution, it becomes imperative that radiation is accurately delivered to the correct place. "Image guidance becomes more and more critical with these types of radiotherapy delivery," he explained.

Changes in patient and tumour anatomy during a fractionated radiation course necessitate imaging between fractions to ensure the treatment remains accurate. "If you're going to deliver radiation 30 times, things are going to change," said Raaymakers. And even during treatment, motion due to breathing, for instance, can create uncertainties in dose delivery. Image guidance can help to mitigate such uncertainties.

Raaymakers described the wide range of options available for guidance of external-beam radiotherapy. In-room CT-on-rails systems offer imaging prior to, although not during, treatment. Megavoltage imaging with treatment beam can be used before or during treatment and provides good bony-anatomy visualization, albeit with low contrast and signal-to-noise ratio. Fluoroscopy systems also offer real-time guidance during irradiation.

Ultrasound can now be employed for treatment guidance, with Elekta's Clarity allowing inter- and intra-fraction imaging, and other systems offering inter-fraction ultrasound guidance. Other approaches include radiofrequency tracking of implanted beacons and on-board cone-beam CT. Further ahead, biological guidance may be possible, enabled by the PET-guided system under development by RefleXion Medical.

Ultimately, MRI may prove the optimal guidance modality, offering real-time visualization of the tumour and its surroundings. As such, several groups worldwide are developing MRI-guided radiotherapy systems. The MRIdian from ViewRay, for example, which is based on three cobalt-60 sources and a 0.35 T MRI, was first used to treat a patient at the start of 2014 and is now in regular clinical use.

The AuroraRT, developed at the University of Alberta, integrates a 6 MV linac with a 0.5 T magnet. The first prototype was operational in December 2008 and the system is now being commercialized by MagnetTx. The Australian MR-linac project is also developing an integrated system, producing an operational prototype in January of this year.

Raaymakers and colleagues at UMC Utrecht, Elekta and Philips have developed a high-field MRI-guided radiotherapy system that integrates a 1.5 T MRI with a 6 MV linac. The first prototype was built in 2009, and a clinical system is now under construction and being commercialized by Elekta under the name Atlantic.

"Image guidance is a major research arena for radiotherapy, and MRI guidance offers great potential," Raaymakers concluded. "Sight during treatment enables better targeting, better sparing and better dose-response assessment."

New horizons in adaptive therapy

Once it is possible to "see what you treat", the next step is to perform adaptive radiotherapy (ART). Katia Parodi from Ludwig-Maximilians-Universität München examined the key ingredients of modern ART, explaining first how the use of graphics processing units (GPUs) to accelerate computation made a huge impact in this field.

GPUs can run accurate Monte Carlo-based VMAT dose calculations in less than 40 s – opening up the possibility of dose recalculation while the patient is on the table. "This could allow us to go towards plan-of-the-day adaptation," noted Parodi. Accelerated dose calculation also applies in particle therapy, where GPU-based Monte Carlo proton calculations have been achieved in less than 4 s per million particles.

Rapid computation also enables the application of advanced planning strategies, such as multi-criteria optimization (MCO), in which multiple plans are calculated and optimized. MCO is already deployed for photons and under development for ions.

Another critical ingredient is in vivo dose reconstruction. "If you can reconstruct the actual delivered dose, this could open a new way to document treatment," said Parodi. "And if you can do this fast enough, it may be even possible to correct the treatment if something is going wrong."

Parodi described some novel methods for in vivo dose reconstruction in photon therapy, including Cerenkov imaging and thermoacoustics. For particle therapy, she highlighted the recent renewed interest in ion-based transmission imaging for planning. Likewise, approaches such as PET, prompt gamma imaging and ionoacoustics are under investigation for monitoring dose delivered during treatment.

Looking forward, Parodi suggests that we may now be entering the era of biological guidance. "The next dimension to explore for ART is biological guidance," she told the delegates. One example is the use of PET for stratification, therapy personalization and response assessment. Including the oxygen-enhancement ratio in ion-beam planning, meanwhile, could enable dose-or-cell-killing painting of inhomogeneous tumours.

Parodi concluded by presenting some emerging methods that exploit biology. These include micro- and minibeam therapies, spatially fractionated approaches designed to spare healthy tissue that have been demonstrated with both photon and proton beams. Another possibility is to use nanoparticles for tumour vascular disruption during radiotherapy.

The next 60 years

The final speaker, Robert Jeraj from the University of Wisconsin, faced the hardest task – predicting the future. For a physicist, this usually involves examining current trends and extrapolating. But the future is not always clear: "Even 10 years ago, people did not predict some discoveries like immunotherapy," he noted.

Jeraj suggested that medical physics is one in spirit with medicine, and may progress along a similar path. He cited the "four P's of medicine": prediction of an individual's disease development; personalized treatment; pre-empting disease before it occurs; and the participation of patients, communities and healthcare providers. This rationale gives rise to the idea of precision medicine, which addresses the highly heterogeneous nature of cancer. In the past, little could be done to tackle this, but the emergence of targeted therapies is bringing personalized therapies within reach.

In a Q&A session held after the symposium at the nearby Hereford Arms, Robert Jeraj shares his thoughts on the future for medical physics.

Unfortunately, there are obstacles to overcome. For example, cancers evolve in time to become harder targets to treat. So how can medical physics help? "We need to capture the whole disease and the evolution of disease, using multi-modality imaging techniques such as optical and molecular imaging," explained Jeraj. In radiation therapy, such a shift from anatomical imaging and population-based treatment to molecular imaging, patient-specific therapies and non-uniform dose delivery is the foundation of "biologically conformal radiotherapy".

Jeraj noted that medical physics must also strive to treat more advanced cancers. He described a case in which PET imaging of a patient with advanced metastatic prostate cancer revealed multiple, extremely heterogeneous, lesion responses: responding, non-responding, stable, emerging and disappearing. "How can you treat this patient with one modality? You can't," he said. But such information would possibly enable selective localized targeting (by radiotherapy, for example) of selective non-drug-responsive lesions. "Radiotherapy can be exploited to big advantage of patients with highly advanced disease."

This idea of extracting large amounts of useful data from a single medical scan is the premise underlying radiomics – a promising emerging field. However, much more data are available from genomic and other tests. To analyse such large amounts of data, says Jeraj, we must learn from "big-science" physics approaches. When analysing data to detect the Higgs boson, for example, CERN physicists relied on a deep understanding of the underlying fundamental physics.

"Likewise, when we move to medicine, we have to understand the underlying biological principles that drive observations," Jeraj explained. Image analysis and modelling of disease require accurate knowledge of the biology. To achieve this effectively, it's essential that physicists partner with biologists. "These problems are way too hard to tackle alone," he said.

With medical physics perhaps on an inevitable path towards incorporating more and more biology, what could the next 60 years hold for PMB? According to Jeraj, by then, the journal may require a name change – to Physics & Biology in Medicine.

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