Judging by the keynote presentations, the end-game in radiotherapy physics is fast coming into focus. Two converging themes are in play. For starters, there's the growing realization that truly adaptive radiotherapy needs to be informed by a more granular understanding of tumour biology, a shift in mindset that points the way to customized dose-painting of tumour subvolumes with very different radiobiological properties. Equally significant is the relentless pace of innovation in structural and functional imaging, with established and emerging modalities yielding "game-changing" improvements across cancer diagnosis, treatment planning, treatment delivery and evaluation of tumour response (during and after treatment).

"If you are able to paint the dose, the question is where to paint...The whole awareness of tumour geometries and movement is driving developments [in radiation-therapy physics]," noted Jan Lagendijk of the University Medical Center Utrecht (the Netherlands) in an opening presentation that asked "Will the future of radiation therapy be MRI-guided interventional radiology?" Lagendijk and colleagues are exploring how online MRI can be used to see where the tumour is, to follow how it moves, and to better define its functional characteristics (e.g. to visualize hypoxia and perfusion) during treatment.

The hope is that real-time MRI guidance will allow radiotherapy treatment plans to be revised as the target moves and morphs, reducing the need for wide safety margins to ensure adequate target coverage. What's more, if the target volume can be identified more precisely during each treatment session, then it should be possible to ramp the dose delivered to the primary tumour and involved lymph nodes.

Lagendijk told delegates how his team is currently optimizing a prototype radiotherapy accelerator with integrated MRI functionality. The system, which is expected to be up and running in January 2009, combines a 1.5 T Achieva MRI scanner from Philips Medical Systems and a 6 MV Elekta Compact accelerator. The group is also exploiting Utrecht's 1.5, 3.0 and 7.0 T MRI simulator systems to assist in its work on MRI-guided prostate brachytherapy using a robotic, single-needle implant device.

Biology lessons

Fellow speaker Suresh Mukherji, MD, professor of radiology, radiation oncology and head and neck at the University of Michigan (Ann Arbor, MI), took up where Lagendijk left off. "Adaptive treatment through the use of IGRT and IMRT is now a reality...We can alter treatment during treatment based on changes in tumour volume or geometry," he told delegates.

Yet Mukherji's keynote presentation, "Physiological and metabolic imaging in head and neck cancer", argued that radiation oncology needs less emphasis on treatment modality and more on biological response. "Let's change the paradigm. Let's begin to see how treatment is progressing at the biological response level...We have the opportunity to identify nonresponding tumours by noninvasively and quantitatively measuring biological response and to use that [information] to adapt treatment."

In effect, Mukherji was making the case for more aggressive utilization of "biological imaging" - technologies like PET-CT, MR spectroscopy, diffusion MR and CT perfusion - to differentiate responders from nonresponders. Diffusion MR is one imaging modality that has a lot to offer in this respect. By tracking the diffusion of water molecules within tissue, the technique can help depict tumour response in the absence of a change in morphology.

Citing an example from his own research, Mukherji explained that apparent-diffusion-coefficient (ADC) values are low in squamous-cell carcinoma (a malignant tumour of squamous epithelium). Herein lies an opportunity: to employ MR diffusion to differentiate between malignant and benign tissue; also to map the heterogeneity of ADC response in the tumour by highlighting how different regions of the tumour respond differently to therapy. "By using ADC to monitor response to treatment, you can see things that you cannot detect on pure anatomical imaging," he concluded.

Into the light

Monitoring response to therapy along the biological/biochemical coordinate turned out to be a recurring theme, one that also featured prominently in the keynote presentation "Optical spectroscopy and imaging in oncology" from Brian Pogue, professor of engineering at Dartmouth College (Hanover, NH).

Pogue kicked off with a look at how researchers are combining optical spectroscopy with established clinical imaging modalities like MRI and CT. The payback? Quantification of molecular tracers and biophysical imaging of tissue via contrast mechanisms that are not otherwise available. "Image-guided optical molecular spectroscopy yields more features and better specificity," Pogue explained.

A case in point is the integration of near-infrared spectroscopy (NIRS) into standard MRI instrumentation. While still very much a work-in-progress, the hope is that optical-MRI interrogation could one day be used to guide therapy or even to individualize the choice of therapy - for example, by providing additional data such as tumour-cell receptor activity in breast-cancer detection and diagnosis.

With this in mind, Pogue and his co-workers at Dartmouth, in collaboration with Philips Medical Systems, have developed a prototype small-animal imaging system that integrates NIRS into a 3 T MR machine. The system also works with a separate breast-biopsy coil for testing in human cancer (with MR for imaging, NIR for spectroscopy). Work is ongoing to enhance image reconstruction and fusion of optical and MR data.

Pogue says the big challenge is getting approval for high-specificity molecular contrast agents that can be used in humans, though initial clinical trial studies are ongoing at some centres. "Preclinical work with fluorescence imaging of glioma tumours using protoporphyrin IX [a protein precursor to haemoglobin] looks very promising," he told medicalphysicsweb. "This hybrid type of imaging can be used in fully diagnostic mode or in an invasive, surgical-guidance mode. In both cases, guiding radiation therapy should prove beneficial to better individual outcomes."

Taken together, the keynote presentations are proof-positive that advances in radiation-therapy physics are on a converging trajectory with the latest innovations in medical imaging and the search for a more granular understanding of tumour biology. Further improvements in clinical outcome will surely follow.

• See Free-form thinking about the future for additional reporting on this workshop.