Center News Magazine: Prolific Partnership Yields Radiation Therapy Advances

Wednesday, October 23, 2013
Pictured: Micheal Zelefsky Radiation oncologist Michael Zelefsky delivers brachytherapy — the placement of radioactive seeds into the prostate gland — with the assistance of an intraoperative CT unit called the O-Arm, which gives real-time snapshots of the prostate.

“There is a unique combination of experts here with the time, effort, and initiative to go beyond the usual,” he explains.

Memorial Sloan Kettering has long been recognized as a pioneer in the treatment of cancer with radiation. The alliance of radiation oncologists and medical physicists has produced the development and clinical implementation of technologies that are now widely used. A noteworthy example of this is intensity-modulated radiation therapy (IMRT), which targets tumors with multiple beams at different angles and intensities. Memorial Sloan Kettering radiation oncologists and medical physicists were leaders in demonstrating the immense clinical value of IMRT

More than 110,000 radiation treatments were given to patients at Memorial Sloan Kettering’s Memorial Hospital and regional outpatient facilities in 2012. Typically, patients have contact with physicians, nurses, and technicians but are not necessarily aware of the experts who play roles behind the scenes in designing and implementing sophisticated treatment plans that kill or shrink tumors while minimizing harm to normal tissue Pictured: Beryl McCormick External-Beam Radiotherapy Service Chief Beryl McCormick and Radiation Oncology Department Chair Simon Powell lead a team that is continually pioneering new methods for treating cancer.

In putting together a treatment plan for an individual patient, radiation oncologists define the target as well as the nearby structures where radiation doses should be minimized. The medical physicists design the best way to execute the plan using mathematical modeling and advanced computer programs, while also monitoring the performance and proper use of the radiotherapy equipment that delivers the treatments. Every plan involves a patient simulation using imaging such as computed tomography (CT), positron emission tomography (PET), magnetic resonance imaging (MRI), or some combination, to map out the treatment area.

“The depth of physics support for radiation oncology here at Memorial Sloan Kettering is unmatched,” says Medical Physics Department Chair Joseph O. Deasy. “Our department is one of the largest and oldest in the world, and the institution has a deep commitment to developing and improving the delivery of radiotherapy as well as solving every technical challenge that we think impacts patient outcomes.”

Beryl McCormick, Chief of the External-Beam Radiotherapy Service, explains that the large number of patients treated at Memorial Sloan Kettering allows radiation oncologists and medical physicists to become very specialized. “Earlier this year, treatment planning became site oriented, meaning that junior-level medical physicists are spending six months being mentored by radiation oncologists and senior-level physicists who focus on designing treatments for one part of the body — for example the breast, or the head and neck — to make them experts in that area.”

Evolving technologies continue to improve both the imaging of cancer and the delivery of radiation. One of the most important advances in radiation therapy has been the emergence of better imaging techniques that make it possible to target tumors with extreme precision and with higher doses of radiation. Recently, novel imaging methods have been brought into treatment sessions so that physicians and technicians are able to monitor in real time the proper positioning of patients and, if necessary, make immediate adjustments.

These enhancements, many of which were developed by Memorial Sloan Kettering medical physicists, have spurred a number of new clinical initiatives led by Memorial Sloan Kettering’s radiation oncologists investigating more-effective approaches — sometimes allowing radiation therapy for tumors that were until recently considered untreatable.

What follows are several examples of the ways in which Memorial Sloan Kettering radiation oncologists and medical physicists are innovating new approaches for treating various cancers.

Prostate Cancer: Missile-Like Delivery of High-Dose Radiation

Memorial Sloan Kettering is recognized worldwide for being a leader in radiation treatment for prostate cancer, having gained the largest experience using IMRT to improve cure rates and quality of life. This expertise with IMRT has served as an important foundation as emerging technologies are developed, refined, and applied in the treatment of patients with the disease.

The SHARP Advantage

With the help of sophisticated image guidance and global positioning system techniques, Memorial Sloan Kettering is now able to offer prostate cancer patients a more focused approach to delivering higher doses of radiation more accurately and in less time than with IMRT. Using a form of radiosurgery called stereotactic hypofractionated accelerated radiation to the prostate (SHARP), physicians can deliver ultrahigh doses of radiation in only five treatment sessions, compared with close to 50 sessions over ten weeks using the conventional approach.

GPS markers called ferromagnetic transponders are implanted by a urologist into the patient’s prostate gland. The beacons act as homing devices, sending out electromagnetic signals of the prostate’s exact location that can be used to guide the linear accelerator, which delivers high-energy radiation to the prostate over several minutes. If the prostate moves outside of a very tight margin, the radiation treatment can be stopped and adjustments made.

“This kind of missile technology helps us and our medical physics colleagues localize the target with an accuracy akin to the sharpness of a surgeon’s scalpel, sculpt a high dose of radiation around the prostate, and effectively minimize the amount of normal tissue that’s included in that margin,” says radiation oncologist Michael J. Zelefsky. “In this way, we can safely give the entire course of radiation in only five treatment sessions with fewer side effects.”

Memorial Sloan Kettering is the only hospital in Manhattan currently offering this treatment approach and one of only a few academic medical centers in the world doing it within the context of an ongoing clinical trial. Despite the application of high radiation doses, the more than 100 patients with disease confined to the prostate who have been treated with SHARP have tolerated the treatment well. After treatment, patients are closely followed with MRIs and a prostate biopsy.

“SHARP will likely replace the standard way of delivering external radiation therapy for prostate cancer if continued research and patient follow-up show that it is equally or more effective,” says Dr. Zelefsky.

Improving Brachytherapy with Intraoperative Image Guidance

Over the past 15 years, Memorial Sloan Kettering has established long-term success rates using brachytherapy — the placement of radioactive seeds into the prostate gland to deliver an extraordinarily high dose of radiation to the tumor.

The depth of physics support for radiation oncology here at Memorial Sloan Kettering is unmatched.

-Joseph Deasy, Department Of Medical Physics

Memorial Sloan Kettering has improved the delivery of brachytherapy by incorporating advanced imaging techniques that are commonly used for diagnostic procedures and treatment planning prior to treatment. In fact, it built the only state-of-the-art intraoperative imaging suite in the country dedicated solely to brachytherapy procedures.

One unique feature of the suite is a portable intraoperative CT unit called the O-Arm, which allows physicians to obtain real-time snapshots of the prostate that are fused with ultrasound images to target and confirm the accuracy of radioactive seed placement during the procedure. Memorial Sloan Kettering is currently the only center in the world routinely using this system during brachytherapy.

Marco Zaider, Head of Brachytherapy Physics, and Gikas S. Mageras, Chief of the Computer Service, led a team that developed a unique, patent-pending computer program that enhances the precision of the procedure by enabling physicians to receive instantaneous feedback about exactly where the seeds should be placed within the prostate gland and giving them the opportunity to make corrections on the spot. Being able to obtain and act on this information while a patient is asleep during the procedure in the operating room reduces the possibility that physicians will have to make adjustments later.

“Another advantage is that we can now safely re-treat patients with prostate tumors that have recurred years after treatment with other modalities by using this pinpointed seed implant approach, presenting a treatment option for these patients that didn’t exist before,” says Dr. Zelefsky, who is Chief of the Brachytherapy Service.

Memorial Sloan Kettering’s intraoperative imaging suite also offers MRI, which shows soft tissue differentiation, and PET/CT, which provides detailed anatomical images. Plans are under way to integrate these tools into a computer navigation system that could be used to further refine seed placement during brachytherapy. This unique combination of advanced imaging tools will enhance treatment planning and delivery as well as tumor assessment after treatment, allowing for more-adaptive therapy in which treatment changes can be made based upon tumor response.

“What makes the prostate program at Memorial Sloan Kettering unique is the availability of this comprehensive package of options we can offer our patients,” says Dr. Zelefsky. “Our expertise and this array of options at our disposal enable us to tailor radiation therapy based on the characteristics and location of the tumor, as well as important physical, emotional, and psychological factors that take the entire individual and his quality of life into account.”

Breast Cancer: Expanding a Treatment’s Reach

Radiation therapy for breast cancer can be a double-edged sword. The treatment is usually given after a breast tumor is removed by surgery to destroy any stray cancer cells that may have been left behind. If there is evidence the disease has spread locally — to the chest wall and nearby lymph nodes but not to distant organs — the chest and multiple nodes must be targeted while minimizing the dose to the lungs and heart.

Even with IMRT, this is a challenging task because too much radiation to the lungs can cause an inflammatory condition known as pneumonitis, while in the heart it can cause thickening and stiffness of muscle tissue and connecting arteries, increasing the risk of heart disease.

The standard IMRT approach has used three to five beams and has provided somewhat patchwork coverage. While the approach helps preserve heart and lung function, the uneven radiation levels — the “hot” and “cold” pockets — increase the risk of missing microscopic disease that could spread.

“If you’re targeting the chest wall and multiple nodes, it gets very complicated to design a way to treat the entire area safely,” says Memorial Sloan Kettering radiation oncologist Alice Y. Ho. “In addition, an increasing percentage of breast cancer patients are having reconstructive surgery and receiving implants, which present a technical challenge to work around.”

Dr. Ho, in collaboration with Dr. Powell, decided to investigate whether spreading the radiation dose over a larger number of beams would make it possible to cover the area more thoroughly without endangering the patient. Working with medical physicists Ase M. Ballangrud-Popovic and Guang Li, they developed a treatment plan using eight to 12 beams that targeted potential disease sites while sculpting the radiation around multiple obstacles in the anatomy.

Pictured: Alice Ho Radiation oncologist Alice Ho helped develop a treatment plan for breast cancer that covers a larger area without endangering the patient.

The approach leaves less margin for error around the targets — being even a few millimeters off can miss cancer cells and greatly undermine results. “This technique has a very steep dosage fall-off, meaning that the radiation drops right off at the edge of the treatment area,” Dr. Ballangrud-Popovic says. “Because of this, we have to make certain the patient is positioned more accurately than with standard therapy.”

To accomplish this, the team employed a new 3D surface imaging system called Align RT®, which uses three cameras in the treatment room to track the surface of the patient in relation to the radiation beam. The system monitors any movement during treatment so adjustments can be made. The Align RT surface images are used in combination with conventional x-ray images that rely on bones as landmarks. Since Align RT does not use radiation to image the patient, it can function continuously during treatment to monitor patient position.

The new IMRT planning approach with use of the Align RT imaging system was recently tested in a pilot study involving 106 breast cancer patients who received the treatment following surgery. Each patient received 25 radiation doses, with some receiving chemotherapy as well. The results show conclusively that delivering radiation using this method has no increase in detectable side effects to the heart or lungs.

The study also suggests the new method may provide some unexpected cosmetic benefits. Because the higher number of beams provides a more evenly spread dose, there are fewer pockets of high radiation that cause red or dark spots in the breast skin. Fibrosis — a scarring and stiffness in the breasts of women with implants — may also be minimized or avoided.

A new study is now planned to look specifically at the question of whether the new IMRT approach produces better results than conventional therapy in women with implants. “It will be significant if we improve the cosmetic appearance of women with implants,” Dr. Ho says. “It has become clear that this is a major concern for patients, so this benefit alone would be very important.”

Pancreatic Cancer: Condensing Treatment Time

Radiation therapy plays a vital role in the treatment of pancreatic cancer. By the time it is detected, the disease has often spread locally, invading important abdominal blood vessels and other adjacent structures and making surgical removal impossible. The standard treatment for this type of tumor — when it has not spread to distant organs — is five and a half weeks of daily radiation, with chemotherapy given before, during, and afterward.

But this regimen can be arduous, particularly for older patients, and it has another drawback: During the radiation period, the strength of the chemotherapy must be reduced to avoid toxicity from the combined treatments. This leaves the patient with a less-aggressive system-wide therapy for more than five weeks.

Memorial Sloan Kettering radiation oncologist Karyn A. Goodman has been investigating stereotactic body radiotherapy (SBRT), a highly precise form of radiation therapy that could shorten treatment time and potentially be more effective. SBRT uses advanced imaging technologies and sophisticated computer guidance to deliver very high doses of radiation directly to tumors. It usually can be given in five or fewer daily sessions. Pictured: Karyn Goodman Medical physicist Ellen Yorke, left, helps radiation oncologist Karyn Goodman plan precisely targeted high-dose radiation treatments for pancreatic cancer.

A clinical trial, conducted jointly by Memorial Sloan Kettering, Stanford University School of Medicine, and Johns Hopkins University School of Medicine, tested the safety of SBRT in approximately 60 patients with inoperable pancreatic cancer that had not spread. The patients were given the chemotherapy drug gemcitabine (Gemzar®), received five SBRT treatments, and then resumed chemotherapy.

The study was recently completed, and results have been very promising. “We found that patients tolerate this treatment well, with minimal side effects,” Dr. Goodman says. “One concern was that the bigger dose of radiation would cause intestinal bleeding because that occurred in prior SBRT studies done elsewhere. But our patients did not experience bleeding, and SBRT appears to extend lifespan.”

New imaging techniques help ensure the patient is in the same position for every session and that the target area does not shift during treatment. Dr. Goodman has collaborated extensively with medical physicist Ellen Yorke to manage patient motion. To minimize the effects of breathing, patients now wear an inflatable abdominal compression belt.

In addition, Drs. Goodman and Yorke worked to incorporate an x-ray imaging technology on the linear accelerator called IMR, which closely monitors the targeted region during radiation sessions. Tiny gold markers are implanted in the patient as landmarks, and IMR tracks any movement of the gold markers as radiation is delivered.

“We have a little circle on a screen showing where the marker is supposed to be, and if it starts to move outside that circle, we know we need to stop and get repositioned,” Dr. Goodman says.

Dr. Goodman continues to use SBRT on appropriate patients, and hopes to test SBRT head-to-head against the standard treatment in a future trial.

Brain Metastasis: Single-Day High-Dose Radiation

Experts at Memorial Sloan Kettering have led efforts to improve and expand the use of radiation therapy for the treatment of brain metastases, a process in which cancer cells break away from a primary tumor and spread to the brain. Memorial Sloan Kettering radiation oncologists and medical physicists have refined the use of sophisticated tools to safely deliver powerful doses of radiation to brain metastases with remarkable precision.

One such technique is stereotactic radiosurgery (SRS). This advanced type of external radiation therapy conforms to the three-dimensional shape and size of a tumor to deliver an intense, highly targeted, and effective dose of radiation with fewer side effects than conventional radiation techniques. For some patients with brain metastases, this single-day, high-dose treatment can replace the daily delivery of lower doses of radiation over a course of therapy that can last up to six weeks.

“The vast majority of the time, SRS can either eliminate metastatic brain tumors or stabilize and shrink them so that they remain inactive after treatment,” explains radiation oncologist Kathryn Beal. “Most patients tolerate the treatment very well, and because it’s typically done in one day it causes very little or no interruption in the delivery of other treatments like chemotherapy.” In addition, many patients can resume their normal activities the day after treatment.

“We’ve been using stereotactic radiosurgery more often over the past several years because we’re getting better at diagnosing brain metastases early, when they’re relatively small and ideal for this therapy. Treating appropriate patients with SRS (versus other therapies) limits side effects and thus improves their quality of life,” says Dr. Beal. The approach has become standard for patients who have three or fewer brain tumors that are 3 centimeters or less in diameter. Other brain tumors such as acoustic neuromas can also be treated with this technique.

A team of medical physicists who are specially trained to calculate the required dosimetry and field design for the delivery of SRS works closely with an array of specialists who are dedicated to caring for people whose cancer has metastasized to the brain. This multi-disciplinary team of experts — which, in addition to radiation oncologists and medical physicists, includes neurosurgeons, neurologists, neuro-radiologists, and expert nursing staff — is among the most experienced in the world, treating hundreds of tumors with SRS annually.

“What makes Memorial Sloan Kettering unique is that many of our patients can benefit from the opportunity to receive SRS in combination with other treatments such as neurosurgery and newly developed cancer drugs, both of which can reduce the risk of cancer recurrence and improve survival and tumor control,” notes Dr. Beal, who is leading research to determine the effectiveness of such treatment combinations.