Understanding ART: Adaptive Radiation Therapy

In using imaging modalities to better define the target at the diagnostic level and to guide the delivery of the dose in treatment, adaptive radiation therapy is changing the paradigm for cancer patients.
Organs of the human body shift in size, shape, and position from week to week as oncology patients react to radiation therapy or as the progression of tumors induces loss of weight. Cancer fighters have known this for some time. Now, however, thanks in part to research conducted at the Comprehensive Cancer Center at the University of California, San Francisco (UCSF), it is understood that organ movement does not always occur in predictable ways. This is a discovery of significant concern for the field of radiation oncology.
Jean Pouliot, PhD, professor in the UCSF department of radiation oncology, says, "Traditionally, radiation treatments have been delivered based on a dose that was planned 2 or 3 weeks earlier; relying on a number of quality-assurance procedures would, it was hoped, provide a dose that, at the time of actual delivery, would be the correct one." Pouliot is a Comprehensive Cancer Center imaging researcher who, for more than a decade, has been working to unlock the secrets that will allow radiation therapy to be administered with greater precision and efficacy. "Because of our new insights into organ movement, we are realizing, to an overwhelming extent, that you cannot obtain a CT study of the patient 2 weeks before treatment and assume that the anatomy that you acquired then will remain unchanged (so that you can position the patient exactly the same way, time after time)," he says. "Moreover, as we now see it, the real endpoint is not only having the patient correctly positioned, it is also ensuring the dose is being primarily delivered to the tumor. That can only be accomplished if you know the positioning information immediately before you treat."

PRINCIPLES

Pouliot and his colleagues at the Comprehensive Cancer Center have devised a collection of innovative tools and techniques to produce that information in just such a timely manner. "The dream of having all the information at the same place, at the same time, for the same patient is now being realized," he says. "We are now able to verify the delivered dose. We are able to base clinical knowledge on the real dose delivered, not on what was planned weeks earlier." These abilities come under the heading of a class of interventions known as adaptive radiation therapy (ART).

"Adaptive radiation therapy is really more of a concept than it is a technology," Pouliot explains, adding that the ideas upon which adaptive radiation therapy is based were first arrived at more than a decade ago, when the requisite technology was still in a nascent stage. Then, for the first few years after adaptive radiation therapy moved from the drawing board to the imaging suite, he adds, "It was technology-driven, but not any more, because it is a concept that can be approached in a number of ways, depending on the technology you favor or have access to for this purpose. Today, what we find is that adaptive radiation therapy is increasingly a dose-driven proposition."

Even so, an imperative continues to be the correct positioning of the patient. The difference now is that the options for establishing positioning have been expanded. "One of the choices is to use the Siemens PRIMATOM, a combination linear accelerator and CT scanner on rails," Pouliot says. "You simply roll the patient into the CT, take a three-dimensional (3D) image, and then roll the patient back to the treatment position and begin administering the dose."
The choice embraced by Pouliot is megavoltage (MV) cone-beam CT, which is currently under clinical research evaluation. Here, a Siemens linear accelerator generating 6 MV beams is paired with an amorphous-silicon electronic portal imaging device.
"We are using the linear accelerator itself as the imaging tool," Pouliot says. "The linear accelerator is rotated around the patient and a portal image is acquired with very low exposure at each angle around a 180 degree arc. This arrangement permits creation of the CT image directly from the beam and, using classic Feldkamp algorithms, allows for volumetric reconstructions with a filtered back-projection. We get an image and verify that the patient is properly positioned and that the anatomy is correct, and then we begin treatment."
MV conebeam CT image of a head phantom with implanted radiopaque markers.

MV conebeam CT image of a head phantom with implanted radiopaque markers.

Evaluation of the proper patient alignment immediately before radiation treatment: The MV conebeam image CT is superimposed on the image from the regular kV planning CT. The positions of the targets (tumors) and organs at risk contours drawn on the planning CT, as well as the treatment beams seen from different views, provide all the required information for the verification and the correction of the proper patient alignment.

APPLICATIONS



Patients with cancers of the head and neck are initially expected to see the most benefit from this approach. "That is primarily because, with cancer in the neck area, there is a significant degree of freedom in terms of rotation and translation," Pouliot notes. His version of adaptive radiation therapy also should prove invaluable as a way of minimizing organ risk. "In the head and neck area there is a great deal of organ risk, given that you have structures there that include the brain stem and the spine," he says. "Obviously, we do not want to deliver radiation to those organs. We want to be able to control radiation delivery meticulously there, and that is precisely what MV cone-beam CT is allowing us to do."
Since cancers of the head and neck typically respond well to radiation therapy, it is thought that the anticipated superior accuracy made possible by MV cone-beam CT will encourage practitioners to use higher doses in that region than are currently recognized as advisable. "If we could deliver higher doses, we would improve survival rates," Pouliot says, "but, at the moment, we cannot increase the dose because of the associated side effects and complications. If we could target the tumor better and avoid the organ risk, there is a real chance to improve survival rates."
Evaluation of the proper patient alignment immediately before radiation treatment: The MV conebeam image CT is superimposed on the image from the regular kV planning CT. The positions of the targets (tumors) and organs at risk contours drawn on the planning CT, as well as the treatment beams seen from different views, provide all the required information for the verification and the correction of the proper patient alignment.
Pouliot expects that MV cone-beam CT will one day be applied, as well, to the treatment of other types of cancer (especially prostate cancer), and will be found effective against them. This expectation may be met soon, as UCSF is poised to begin a small-scale clinical trial of MV cone-beam CT. "The first phase of the study will involve a cohort of just 10 patients," Pouliot says. He will serve as lead investigator of the single-site endeavor. "Each patient will probably be imaged several times to give us, perhaps, 50 initial data sets of complete two-dimensional (2D) and 3D images. Later, we intend to determine the protocols that will allow us to have a clinical impact."
With this study, Pouliot wants to move toward answering several relevant questions. "Today, we can image the complete anatomy in 3D, whereas, before, it was just 2D imaging," he begins. "That gives us a lot more information, but the real questions are how we can best use that information and what we gain from that. How is human perception improved? Can we improve the speed with which an error is detected? After studying these issues in the first phase of the investigation, our attention will turn to another round of questions. Specifically, now that you know exactly where to deliver your dose, do you want to increase the dose to the tumor, or do you want to reduce the dose to the surrounding tissues?"
PRECISION IN TREATMENT
In time, MV cone-beam CT and other forms of adaptive radiation therapy may permit highly individualized treatment of cancer patients through customized dose delivery. "Adaptive radiation therapy is not the end point in all this," Pouliot says. "The first phase was to develop a number of tools to improve precision in delivery. Intensity-modulated radiation therapy (IMRT) was the key player in that. We can now control the dose to a significant extent."
"The second phase is adaptive radiation therapy: what we are doing now, using imaging modalities to guide the delivery of the dose, and also using other imaging modalities at the diagnostic level to define the target better. The third phase, still in the future, for the most part, is functional or molecular imaging. This will allow us to differentiate which part of a tumor is the most aggressive, which part of the organ really has cancer, and which is healthy tissue. IMRT and adaptive radiation therapy will be used to target the tumor better, based on functional and molecular imaging using MRI and PET/CT imaging."
Once these modalities are in routine use, adaptive radiation therapy will provide the framework for using the collected information, Pouliot adds. "We will not be talking about adaptive radiation therapy as a stand-alone treatment. Right now, we administer the same total dose for all patients within the same group of cancers. As we learn more about dose response from functional imaging, for instance, we will be able to stop treatment earlier for patients who respond well to radiation. Conversely, we will be able to extend treatment for certain individuals beyond the recommended limit, if necessary, to ensure that all cancer cells have been killed." Pouliot concludes, "It will all be possible thanks to having the fully up-to-the-moment information needed so that tumors can be targeted better and doses can be delivered far more accurately."

Cellular phone use and brain tumor; What is the REAL story?

Cellular phones and cancer are in the news all the time now it seems. But almost everyone uses cell phones. All over the world, tens of millions of people are pressing them against their heads for hours every day. In the U.S. it is estimated that there were at least 100 million cell phone users, as of early 2002, and that number has continued to climb.
So what's the fuss? Is cancer caused by cell phones a serious concern, or the media's panic-du-jour?
A cell phone, and a household cordless phone, use a low level form of microwave radiation to send and receive their signals. Microwaves, as you know, are used to cook food. As the radiation penetrates tissue it causes it to heat.
Is this a problem for us with cell phones? That is the current debate. Let's examine the positions and the known evidence, without hype or prejudice. As always, EHSO will provide citations and links to the sources of any evidence provided, so you can verify it for yourself.

Cell phones are dangerous:

They emit microwaves.
You hold the source of the emission against your brain
There are claims that people have had brain tumors in the exact size, shape and position as the antenna on their cell phone.

Cell phones are safe:

Cell phones use a very, very low level of radio frequency (rf) energy - too low to cause damage.
The type of energy emitted is non-ionizing - meaning it doesn't cause damage to chemical bonds or DNA.
Hundreds of millions of people have been using cell phones and cordless phones for years. If there were a problem, we would have seen it by now.

What is the radiation produced by a cell phone?

Like televisions, alarm systems, computers, and all other electrical devices, Cell phones (also called mobile phones) are radio devices that use Radiofrequency (Rf) energy emit electromagnetic radiation. They operate at low power (less than 1 watt) by transmitting and receiving electromagnetic radiation in the radiofrequency (RF) end of the spectrum. Radiation which is called "ionizing" can be absorbed by tissue and break molecules apart, such as gamma rays and x-rays, are known to cause cancer. The concern is that the cell phone and it's antenna (the source of the radiation) are held close against the head)

The damage to the DNA molecules is thought to be the cause. The radiation that a cell phone uses is also part of the same electromagnetic spectrum, but is not ionizing. For this reason, the US FDA can regulate these devices to ensure that the radiation doesn't pose a health hazard to users, but only once the existence of a public health hazard has been established. RF energy was mistakenly thought to similarly cause cancer.

Scientific Studies

Some mobile phone users have been diagnosed with brain cancer, and many others who have not used mobile phones have gotten the disease, too. Each year in the United States, brain cancer occurs at a rate of about six new cases per 100,000 people. Among the 100 million Americans who own mobile phones, then, about 6,000 cases of brain cancer would be expected among them in a year, even if they had not used mobile phones.
Scientific studies have focused on the question of whether the statistical risk of getting brain cancer is increased in those who use mobile phones compared to non-users, leaving to the courts the judgment of whether Chris Newman or other individuals would have gotten the disease had they not used a cell phone.

Perceptions and Concerns

The latest studies may support the generally held position that cell phone radiation is not a substantial hazard, but they will never be able to prove cell phones to be absolutely safe. It is logically impossible to prove a negative, that cell phones can not cause cancer.

Conclusions

EHSO has seen no credible evidence to date that cell phones cause cancer or brain tumors. It is illogical to believe that evidence of unusual brain tumors is covered up when there are hundred's of millions of people using cell phones worldwide. There is a TREMENDOUS amount of junk science and thoroughly ignorant (as in untrained, uneducated) people running around naming themselves as experts and publishing their opinions on the internet. This hype and fear-mongering has only one goal: to puff up the egos and wallets of those propagating nonsense.
However, cell phones are still relatively new, and while science does not support that the radiation may not be likely to cause cancer, time may prove differently! And in any case, it may cause some other type of damage (certainly accidents in cars from being distracted while fumbling with the phone!)
So common sense suggests that we each take some prudent precautions.

Precautionary Steps To Take

There are some simple steps that cell phone users can take to reduce any remaining risk:
First, use a headset or speakerphone mode. That moves the phone (and it's antenna) away from your head.
Second, consider reserving the use of mobile phones for shorter conversations or when a conventional phone is not available.
Third, the effects of cellular damage are greatest on growing, developing organisms (i.e., the young), so limit children's use of cell phones!
Finally, in a car, use an external antenna mounted outside the vehicle to move the source of the radiation farther from you!
And don't believe the claims of conmen preying on people's fear of radiation, selling fraudulent devices that they say protect against radiation. These useless items are mostly sold as "shields" on the Internet. Experts says none of these devices work.
To reduce the risk of an accident while driving, here's a simple tip: enter the several numbers you call the most often in a way that brings them to the top of the list, so you can use fewer keystrokes to dial them. For example, the Motorola V60 starts with an alphabetized list when you press the multi-function button; so start your most commonly called number with "AAA", Like "AAAParents" and the next number with "AAB", like "AABHusband", then they will always appear at the top of the list, which should take fewer keystrokes and less time to dial!

major advance in cancer radiotherapy

Radical improvements in outcome for many cancer sufferers are in prospect following one of the most significant advances in radiotherapy since x-rays were first used to treat a tumour in 1904. The use of charged particles as an alternative to x-ray or gamma ray radiation can extend the scope of radiotherapy to tumours previously requiring invasive surgery, while speeding up diagnosis and reducing collateral damage to surrounding tissue.

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This fast emerging field of charged particle cancer therapy was thrashed out at a recent workshop organised by the European Science Foundation (ESF), which discussed new instruments that will lead to improvements in both diagnosis and treatment. Diagnosis and treatment are closely linked in radiotherapy, since more accurate location of tumour cells in turn enables the radiation dose to be more precisely focused.

"Developments in imaging have allowed improvements in radiation beam placement, and the two areas tend to go together," said Barbara Camanzi, convenor of the ESF workshop, and specialist in radiotherapy instrumentation at the Rutherford Appleton Laboratory Department of Particle Physics near Oxford in the UK. This in turn improves prospects of destroying the tumour while reducing collateral damage to healthy tissue nearby. Such collateral damage causes not just tissue death, but can lead to induction of secondary tumours, which has been a long standing problem for traditional radiotherapy using x rays. Some tissue cells close to the tumour receive enough radiation to trigger mutations in their DNA that can cause them to become malignant, but not enough radiation to kill them. "The fall in collateral radiation deposition in the body ranges from a factor of 2 to 15 depending on the precise treatment indication and body site," noted Bleddyn Jones, an oncologist attending the ESF workshop, from the Gray Institute for Radiation Oncology and Biology in Oxford, UK. "All techniques using external gamma rays and x-rays impart a larger dose to surrounding healthy tissue with long term risks of functional changes and malignant induction."

The improved imaging made possible by use of charged particles also makes it easier to detect tumours when they are small, improving prospects for patients whether or not they actually undergo radiotherapy. "Making an earlier diagnosis of a smaller cancer increases the chance of cure following either particle beam therapy or surgery," said Camanzi.

However, the ESF workshop identified that further significant improvements in instrumentation were required, both for treatment and diagnosis, to exploit the full potential of charged particles for cancer therapy. Further work was also required to adjust dose to minimise the risk of secondary tumour formation caused by the radiation, which remains a risk with use of charged particles. The ESF workshop also addressed the need for improved design of the gantry systems used both for imaging and to deliver the radiation doses in treatment.

The other important issue addressed by the ESF workshop is educating radiotherapy consultants in the new techniques so that they are in a position to determine the best form of treatment for each individual case. Sometimes charged therapy may be the best method, in other cases traditional x-ray therapy, and in yet others surgery or chemotherapy, or combinations of these.

"There is a need to hold more educational and training meetings on particle therapy especially in those European countries that at present have no plans for such facilities," said Camanzi, who noted that a follow up symposium in Oxford had been proposed for 2010.

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Adapted from materials provided by European Science Foundation.