A moving target problem
Tumor motion, due to respiration, peristalsis and organ deformation severely limits the effectiveness of radiation therapy.  To compensate for tumor location uncertainty due to motion, safety margins are typically added to the prescribed tumor volume prior to treatment. 

Tumor motion due to respiration

                                Tumor motion due to respiration

Due to these increased margins, the total desired radiation dose must be delivered over a series of smaller fractions (typically 30-40, over a 5 week period) in order to minimize toxicity to healthy tissue surrounding the tumor.  Radiation oncologists are therefore faced with the following trade-off:   

    "Maximizing dose to tumor for higher cure rates while minimizing collateral damage to healthy tissue"

Existing motion solutions do not extend to multiple-targets
Many attempts to solve the tumor-motion problem (and safely increase dose to tumor) are commercially available or under development, including:  X-ray guided therapy, respiratory gating, implantable beacons and MRI-guided therapy.  Unfortunately, these methods have serious drawbacks and limitations:

• X-ray imaging has poor soft-tissue contrast.  Most existing systems rely on tracking fiducial markers or bony anatomy to predict tumor location
• Respiratory gating is ineffective, since the breathing cycle is variable in nature (aperiodic and hysteretic)
• Fiducials and beacons are not applicable for all patients since they introduce complication risks. Moreover, implantable markers can migrate relative to the tumor during the treatment course.
• Low-field MRI generally results in poor quality volumetric images, while higher field MRI can introduce dose "hot-spots" outside of the target volume due to the electron return effect.

Most importantly, while the above methods can be successfully used for patients who present with early-stage cancer, they are too cumbersome and complex to use when treating later-stage patients who have multiple disease sites.

PET is promising but is not currently used during treatment
Positron Emission Tomography (PET) is emerging as the imaging standard in cancer detection and diagnosis, offering higher sensitivity and specificity compared to all other imaging modalities across the majority of cancer types.  With the use of a radio-labeled tracer called FDG, PET depicts metabolic activity, and causes tumors to “light up”.  Other PET tracers such as F-MISO and FLT can identify distinct characteristics of tumors such as hypoxia and cellular proliferation.

                                CT Image                                                                      FDG-PET Image             

The combination of PET and radiotherapy has significant potential, since signals originating from tumors throughout the body can be harnessed directly to adapt treatment.  However, until now PET has not been incorporated into treatment delivery since it takes minutes to generate a reasonable quality image and therefore, is unsuitable to compensate for motion caused by respiration and other bodily functions.