Volume 35, Issue 6, June 2008
Index of content:
- Joint Imaging/Therapy Symposium: Auditorium C
Targeting Using Surrogates
35(2008); http://dx.doi.org/10.1118/1.2962351View Description Hide Description
While technology for image guided radiotherapy(IGRT) has advanced dramatically over the past few years, the basic fact remains that the actual treated target remains poorly or not at all visible using most in‐room imaging technologies. As a result, target localization and tracking is typically performed via the use of surrogates of the tumor. These surrogates may be endogenous to the patient (e.g. skeletal anatomy, diaphragm, external surface indicators), or exogenous and introduced into the patient to aid in localization / tracking (e.g. implanted radiopaque or electromagnetic fiducial markers).
The selection of a surrogate should take into account the dynamic relationship between reference information and tumor position / configuration, and immobilization techniques (especially for breathing) may further aid in the fidelity of a given anatomic surrogate.
Implanted markers carry a number of special considerations, including selection of marker, implant location and technique, clinical implications and marker stability over the time course of treatment, reference identification method, and guidance technique. As the vast majority of implanted marker methods have been developed on an ad hoc basis, a systematic discussion of these methods and related considerations can significantly help to guide medical physicists.
1. To discuss the various types of tumor surrogates, both anatomical and implanted, used for radiation therapy targeting.
2. To discuss techniques for identifying or implanting surrogates.
3. To discuss in‐room localization or imaging techniques for different surrogates, including the relationship between immobilization and surrogate fidelity.
4. To discuss the application of different surrogates, clinical feasibility and efficacy, and limitations.
5. To discuss quality assurance procedures and programs.
6. To discuss current challenges and future directions.
Small Animal IGRT: Systems and Studies
35(2008); http://dx.doi.org/10.1118/1.2962447View Description Hide Description
Translational research in radiation oncology has been in some ways limited by the lack of small animal model systems of common clinical issues. New technology, required to deliver ‘clinically equivalent’ radiation at small animal scale, has been developed to compliment existing small animalimaging systems. In support of such activities, two image‐guided small animal irradiation systems have been developed at Princess Margaret Hospital. Both use a 225 kVp x‐ray tube for treatment and include cone‐beam CT capabilities. Work is underway to refine hardware (collimation and animal immobilization) and software (image registration and dose calculation) systems. Multiple experimental models are being developed to exploit these novel technologies including exploration of tumor control and normal tissue toxicity in lung, brain, and other sites.
35(2008); http://dx.doi.org/10.1118/1.2962448View Description Hide Description
While small animal models of cancer have evolved to more closely resemble the corresponding human disease, radiation therapy (RT) techniques for small animals are dramatically different than those routinely used in the clinic. Recently there has been considerable interest in developing conformal radiotherapy methods for small animals so as to incorporate more clinically‐relevant treatment modalities into laboratory studies of cancer.
An attractive approach to this engineering problem is to add radiotherapy capabilities to a micro‐computed tomography (microCT) scanner. This strategy exploits the high imaging performance of existing microCT units in order to produce a small animalimage‐guidedradiation therapy(IGRT) system employing a single X‐ray beam for imaging and treatment. If successful, this small animalIGRT option could be made available as an add‐on option to existing commercial microCT scanners, allowing widespread adoption of small animal conformal radiotherapy throughout the research community.
Initial experiments demonstrated that the dose rate of a GE microCT system is suitable for delivering therapeutic radiationdoses in reasonable treatment times. A variable aperture collimator capable of restricting the microCT X‐ray beam to a variable pseudo‐circular profile has been developed and evaluated. This prototype microCT/RT system is now online for experimental use, and is currently being applied towards a variety of biological studies.
In this lecture I will briefly describe the current status and future work for this approach to small animal conformal radiotherapy. I will then discuss initial biological applications of this system, including treatment of orthotopic models of disease and evaluation of positron emission tomography (PET)‐guided radiotherapy strategies.
At the end of this lecture, the audience will be able to:
1. Describe the relative advantages and disadvantages of developing small animalradiotherapy within the context of existing microCT scanners.
2. Identify biological applications of small animalIGRT where existing small animal irradiation techniques are inadequate, and
3. Discuss the use of small animalIGRT as both a tool for small animal research and a method for conducting clinical trials in an experimental setting.
35(2008); http://dx.doi.org/10.1118/1.2962449View Description Hide Description
The prototype small‐animal irradiator (microRT) developed at Washington University utilizes the commercial 192Ir high‐dose rate (HDR) remote afterloader source in a teletherapy geometry. The system consists of a set of four Tungstencollimators (5.5 mm diameter hole) mounted to an Aluminum support tube. An HDR catheter is used to transport the source to the collimator and pre‐determined dwell positions center the source at the collimator hole. The mouse is placed on a couch that contains a series of drilled holes that act as fiducial localization marks visible on computed tomography(CT)imaging. For most experiments, the mouse is first anesthetized and placed on a couch. The couch is imaged using a commercial CT scanner (spatial resolution approximately 0.6 mm). The couch geometry is automatically registered in the treatment planningsoftware, which was written in the Computational Environment for Radiotherapy Research (CERR) platform. The treatment planner determines the dose and adjusts the source‐to‐target distance to achieve the required field size and the target dose, coupled with the source strength, determines the irradiation time. The couch is mounted to a computer‐controlled three‐dimensional stage that positions the mouse to submillimeter accuracy. Advantages of the system include its relatively high precision, low fabrication cost, and straightforward and robust operation. Disadvantages include the need for having a commercial HDR source and the associated complexities of scheduling experiments, the relatively poor penumbra, and the steep depth‐dose behavior. The system works very well for parallel‐opposed fields to either the whole brain or hemi‐brain, and tumors grown on the mouse flank.
35(2008); http://dx.doi.org/10.1118/1.2962450View Description Hide Description
Over the past 2 decades, there has been a widening technological disparity between laboratory radiation research and clinical radiation therapy. Whereas simple single beam/single fraction techniques are commonly used to irradiate laboratory animals, advanced three‐dimensional (3D) and computer‐controlled delivery technologies are now used clinically to pinpoint fractionated conformal radiation therapy (CRT) and intensity modulated radiation therapy(IMRT). The technological disparity presents a difficult hurdle in the development of novel treatment methods that combine conformal irradiation and other therapeutic agents. There is clearly a pressing need to bridge the technological gap between laboratory radiation research and human treatment methods.
To that end, we have constructed a Small Animal Radiation Research Platform (SARRP) which integrates imaging,radiation delivery and treatment planning capabilities. The SARRP spans 3 ft × 4 ft × 6 ft (W×L×H). A dual‐focal (0.4 mm and 3.0 mm) spot, constant voltage x‐ray source is mounted on isocentric gantry. The source to isocenter distance is 35 cm. Eighty to 100 kVp x‐rays from the smaller focal spot are used for imaging. Both focal spots operate at 225 kVp for irradiation. Robotic translate/rotate stages are used to position the animal. A novel configuration is devised for CBCTimaging by rotating the horizontal animal between the x‐ray source and a flat panel amorphous silicon detector that are fixed at opposite horizontal positions of 90° and 270° respectively. Radiation beams ranging from 0.5 mm in diameter to (60 × 60) mm2 are available. Conformal dose distributions are delivered using a combination of gantry and robotic stage motion. Treatment planning is performed at sub‐mm resolution where Monte Carlo dose calculations are coupled to a research Pinnacle system for visualization. Depending on filtration, the isocenter dose outputs at 1 cm depth in water range from 22 to 375 cGy/min from the smallest to the largest radiation fields. The 20% to 80% dose fall‐off spans 0.16 mm. CBCT with (0.55 × 0.55 × 0.55) mm3 voxel resolution is acquired with less than 1 cGy in 4 min. The ability of our system to focally irradiate a specific anatomic region or target in a mouse subject has generated exciting new collaborations between laboratory and translational research. These include the study of the response of normal tissue and tumor to focal radiation injuries; the development of molecular imaging markers for early assessment of radiation induced toxicity in the lungs; and the study of molecularly targeted therapy in combination with radiation. We are hopeful that our SARRP, and other similar initiatives, will serve to provide the timely and powerful technology to greatly transform future cancertreatment.
1. Appreciate the disparity between animal radiation research methods and clinical treatment.
2. Understand the challenges in down‐sizing human treatment methods for small animal.
35(2008); http://dx.doi.org/10.1118/1.2962452View Description Hide Description
The significant role of radiation therapy in the management of cancer requires that we advance our understanding of this powerful therapeutic modality. The advancements in imaging and radiation delivery technology promise to make this intervention more patient specific with design of therapy based upon biological image signals and, furthermore, routine redesign as the therapy progresses. This complex interplay between the radiotherapeutic insult and the evolving biological processes will stress current models of RT effect and, ultimately, the current weak models will limit the potential for full exploitation of RT. The development small animal irradiators represent an important initiative to improve our understanding of RT. These developments are occurring as the basic cancer research field is challenging in‐vitro and non‐orthotopic assessments of radio‐effect. Furthermore, image‐based methods of evaluating the microenvironment are being recognized as necessary inputs to normalize the results of RT intervention. These trends suggest that animal irradiation systems are likely to play a central role in the development of robust models of radiotherapy effect.
IMRT Targeting: From Anatomy to Physiology
35(2008); http://dx.doi.org/10.1118/1.2962742View Description Hide Description
35(2008); http://dx.doi.org/10.1118/1.2962743View Description Hide Description
Purpose: Hypoxia renders tumor cells radioresistant; limits locoregional control(LRC) from radiation therapy.IMRT allows targeting of the gross tumor volume(GTV) and can potentially deliver a higher dose to hypoxic subvolumes(GTVh) while sparing normal tissues. This study examines the feasibility of PET/CT‐guided IMRT with the goal to maximally escalate the dose to radioresistant hypoxic zones in a cohort of HNCA patients. Materials and Methods: was administered IV for PETimaging.CT simulation, FDG PET/CT, and PET/CT scans were co‐registered using the same immobilization. Tumor boundaries were defined by clinical examination and available imaging including FDG PET/CT. Regions of elevated uptake within the FDG PET/CT GTV were targeted for IMRT boost. Additional targets/normal structures were contoured/transferred to treatment planning to generate PET/CT‐guided IMRT plans. Results: The heterogeneous distribution of within the GTV demonstrated variable levels of hypoxia within the tumor. Plans directed at performing PET/CT‐guided IMRT for 10 HNCA patients achieved 84 Gy to GTVh, 70Gy to GTV, without exceeding normal tissue tolerance. We further attempted to deliver 105 Gy to GTVh for two patients and were successful in one with normal tissue sparing. Conclusion: It was feasible to dose escalate GTVh to 84 Gy in all 10 patients and in one patient to 105 Gy without exceeding normal tissue tolerance. This information provided important data for subsequent hypoxia‐guided IMRT trials with the goal of further improving LRC in HNCA.
35(2008); http://dx.doi.org/10.1118/1.2962744View Description Hide Description