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Centers Around the World “On Board” with The needs of every radiation oncology practice are as diverse as the patients they serve. No two cancer cases are alike, and the days of the “one-size-fits-all” treatments are rapidly coming to an end.4 Supplement sponsored by an educational grant from Varian Medical Systems Centers Around the World “On Board” with Varian IGRT Speed, precision and versatility are at the perfectly reasonable dose distribution, while lesions require non-co-planar beams in heart of Varian’s technology for image- other order to adequately protect sensitive tissues and guided radiotherapy (IGRT). This article organs nearby. Varian technology is designed to highlights some select case examples enable the best possible treatment for any set of clinical circumstances. that show how clinicians are taking full advantage to provide their patients with LUNG CANCER Adapting the Treatment as the optimal treatments. Tumor Responds Varian’s approach to image-guided radiotherapy utilizes a spectrum of imaging and motion management technologies to pinpoint and target tumors with tremendous speed and accuracy, rapidly changing the outlook for cancer treatment around the world. These include Varian’s On-Board Imager® (OBI) device for generating high-resolution radiographic, fluoroscopic and cone-beam CT kV images right at the treatment machine, as well as the Real-Time Position Management (RPM) system for respiratory gating and motion management during treatment. Outfitted with these image-guidance tools, a Varian Trilogy® or Clinac® iX accelerator offers doctors many choices for treating different disease types. This versatility turns out to be clinically important, enabling doctors to choose between different treatment approaches according to the dictates of a particular situation. For example: The optimal approach for treating one patient with a small lung tumor might be to use a gated 10-field stereotactic body radiotherapy (SBRT) treatment delivered over three fractions of 20 Gy each, based on radiographic images of an implanted fiducial marker. For another patient with a larger lung lesion, it might make more sense to use a conventional six-week schedule to deliver 1.8 Gy per fraction, to allow more recovery time for the limited normal lung volume that remains. In the latter case, implanted markers might be contraindicated, and cone-beam CT imaging could be used to localize the target and to track tumor response over time. Similarly, for some lesions, a simple IMRT treatment delivered with co-planar beams might yield a TM 2 Varian Medical Systems | October 2007 Vasudha Lingareddy, MD, medical director of radiation oncology at the Edward Cancer Center in Naperville, Ill. uses Varian’s Trilogy accelerator for adaptive stereotactic body radiotherapy (SBRT) in exceptionally difficult lung cancers. Treatment plans are adapted as the patient’s tumor responds to treatment and changes in volume. Cone-beam CT imaging makes this possible. A recent case involved a 69-year-old female patient with a sizeable small-cell lung cancer tumor that was growing quickly. “Her respiration was becoming seriously compromised, so we started radiotherapy immediately to reduce the tumor volume,” explains Lingareddy. Lingareddy’s clinical team used the kV-MV image matching feature of the On-Board Imager each day to position the patient for treatment. No fiducial markers were placed into the target area, so the matching was accomplished based on clearly visible soft tissue and bony structures. The PortalVision™ MV imager was used in cine mode on the first two days of treatment to analyze the respiratory motion and make sure that treatment margins were adequate. Since then, Lingareddy says, Edward Hospital has added 4D-CT imaging as well as RPM™ respiratory gating, so she can incorporate tumor motion into her treatment plans and gate the beam during these types of treatment. Lingareddy prescribed delivery of 1.8 Gy per fraction, keeping the dose low to protect surrounding lung tissue because of the volume of the tumor and also because the patient was receiving a concurrent course of chemotherapy. After a couple of weeks, when the patient’s lungs were reaching 16 Gy, cone-beam CT images revealed that the tumor had shrunk sufficiently for Lingareddy to significantly reduce the area being treated. “We checked at that point because, beyond 20 Gy, normal healthy lung tissue can be compromised,” Lingareddy says. “We were able to shrink the field size from 13.2 by 14.6 centimeters down to 11 by 9 centimeters. That’s a reduction in volume of over 75 percent, from 450 cubic centimeters to 104.6 cubic centimeters.” Two weeks later, the clinical team created yet another treatment plan to better protect the patient’s spinal cord, which was approaching its maximum dose tolerance. When all three of the plans were summed, only 21 percent of the pa- LEFT | Image taken at the start of treatment shows complete occlusion of the right lung. Note the impossibility of distinguishing between the tumor and other lung tissues. RIGHT | Image taken approximately two weeks into treatment shows considerable tumor regression. A new plan could be adopted to protect more healthy lung tissue. Centers Around the World “On Board” with Varian IGRT tient’s normal lung tissues had received 20 Gy or more. Had Lingareddy stayed with her first plan, nearly 40 percent of the lung tissue would have reached that dose, and that would have been too much. “Making those adaptations enabled us to save more of her normal lung tissues,” Lingareddy says. “It meant the difference between being oxygen-dependent or not.” Gating the Beam to Manage Motion Doctors at the University of Pittsburgh Medical Center (UPMC) are using Trilogy with the RPM™ system to adapt to intrafraction tumor motion during treatment. Dwight Heron, MD, associate professor and vice chair of clinical affairs in UPMC’s department of radiation oncology, describes the case of a lung cancer patient in her mid-50s, for whom the RPM system was used to synchronize beam delivery with her natural breathing cycle. The On-Board Imager in fluoroscopic mode made it possible to check the gating strategy to make sure tumor motion stayed consistent day to day. “We set our RPM system to deliver the treatment beam only when her tumor moved the least during her respiratory cycle,” Heron says. “When she was about halfway through her exhalation, the tumor was virtually motionless so we could target it very accurately and decrease the treatment margin to half a centimeter. We were also able to couple her gated treatments with an IMRT plan that further decreased the radiation dose to nearby ABOVE | Dr. Heron and Gregory Ross, MBA, the departmental administrator at the University of Pittsburgh Medical Center, review anatomical images. critical structures. This resulted in minimal treat- of verification and the next three just before each ment-related toxicities.” treatment. “The cone-beam CT images give me a lot Hypofractionated Treatments of confidence when I’m getting ready to deliver At other centers, use of Varian’s Trilogy accel- 20 Gy to a patient in one session,” he says. “You erator is enabling a hypofractionated approach, are always going to have some set-up variation no delivering stereotactic body radiotherapy (SBRT) matter what you do to position and immobilize in the treatment of certain early-stage lung tu- the patient. With cone-beam CT, we can adjust for mors, following an RTOG protocol to determine that by placing the isocenter directly in the middle patients’ eligibility for this treatment. Bo Lu, MD, of the tumor. I know what I am doing, with the PhD, radiation oncologist with the Vanderbilt- cone-beam CT images right in front of me.” Ingram Cancer Center at Vanderbilt University Jeffrey Bradley, MD, associate professor of radiin Nashville Tenn., is delivering a total of 60 Gy ation oncology at Washington University School of in three fractions at 20 Gy each. Each patient re- Medicine in St. Louis, uses a similar SBRT protoceives four cone-beam CT scans, one at the time col. One of his patients, a 68-year-old former smoker, already had emphysema and had been hospitalized with congestive heart failure when clinicians discovered a tumor growing in her right lung. “A patient with respiratory disease does not have much healthy lung to spare,” explains Bradley. “This kind of situation tends to make a patient ineligible for invasive surgery to remove the tumor.” Bradley successfully delivered treatment in three fractions over the course of a week. “With our machine I can set the patient up for treatment, LEFT | A highly conformal treatment plan for treating lung cancer with respiratory gating. generate CT images to verify the location of the tumor, and make any needed positioning adjustRIGHT | Cone-beam CT images of the lung are compared with CT images from the treatment plan in order to position the patient accurately for treatment. ments prior to treatment, all right there in one October 2007 | Varian Medical Systems 3 Centers Around the World “On Board” with Varian IGRT place,” he says. “The patient is on the table for less than half the time we would have needed with our earlier protocols.” At Florida’s Melbourne Internal Medical Associates (MIMA) Cancer Center, clinicians have been using Varian IGRT to treat stage III lung lesions. “You cannot name a cancer that I do not treat with Trilogy, whereas I can name some cancers, such as stage III lung, for which certain other radiosurgery treatment devices cannot be used,” says Todd Scarbrough, MD, radiation oncologist and director of the MIMA Cancer Center. “With Trilogy, if you can see the tumor you can treat it, whether it is the size of a pencil point or a football.” “You cannot name a cancer that I do not treat with Trilogy... - Todd Scarbrough, MD “ Radiosurgery tools that shape the treatment beam only with conical collimators cannot be used to treat large tumors or lesions. A Trilogy machine shapes the beam with either a cone or with Varian’s high-resolution Millennium™ multileaf collimator, which can create apertures of nearly any shape or size. “Most radiosurgery systems can paint pretty radiation doses inside a patient’s body,” says Scarbrough, “but the conebased approach is like airbrushing one pixel at a time. With Trilogy, we can saturate larger areas much more quickly and still get precise conformality. It is the difference between slow airbrushing and fast laser printing.” external beam prostate cancer patients using cone-beam CT imaging. “We place three fiducial markers in the prostate prior to the treatment planning CT simulation,” he explains. “Knowing their relationship to the prostate enables us to adjust the target center for daily variations in the prostate position. We truly appreciate the exactness and ease of matching prostate fiducial markers using the 2D-2D marker match feature of the On-Board Imager. We now have ABOVE | Dr. James McGee is pictured with W. Gregg Devanna, the confidence needed to tighten the cheif medical physicist at OSF Saint Francis Medical Center. IMRT margins and escalate the doses to the prostate,” he says. “We also recognize the importance of the selec- because all 240 patients were treated to a very high tive use of the cone-beam CT (CBCT) images in dose of 81 Gy. If these outcomes hold over time, checking for rectal movement into the portal in pa- Scarbrough said, then seed marker–based IGRT tients whose seminal vesicles are also being treat- will have yielded “some of the lowest toxicity rates ed,” McGee adds. “Further, the CBCT can be used of any of the definitive local treatments for prostate daily if a patient declines marker placement.” cancer.” Over at MIMA, Scarbrough and his colleagues recently completed a study of the toxicity outcomes HEAD AND NECK CANCER of 240 patients who were treated for prostate cancer using IGRT. Implanted seed markers were used on At Stanford University in Palo Alto, Calif., a daily basis during treatment to correct for the set- radiation oncologist Billy W. Loo Jr., MD, PhD, up and targeting errors inherent in external beam has been using Varian IGRT to treat cancers of the radiotherapy of the prostate. head and neck, where the major challenge is the “At a median follow-up of 1.4 years, 98 percent very close proximity to critical and highly radiaof our patients showed grade 0 rectal toxicity, and tion-sensitive tissue. “To treat head and neck cannone showed grade 3 or greater toxicities of any cers, we need an especially high degree of precisort,” says Scarbrough. This is particularly notable sion in our treatment,” says Loo. “The On-Board PROSTATE CANCER A number of treatment centers use Varian IGRT as the treatment of choice for their prostate cancer patients. At OSF Saint Francis Medical Center in Peoria, Ill., James McGee, MD, medical director of radiation oncology, preferentially treats all curative 4 Varian Medical Systems | October 2007 LEFT | A color-wash representation of an IMRT plan for treating prostate cancer, shows how the radiation dose will be distributed in and around the prostate. RIGHT | Cone-beam CT images of the prostate (right column) are compared with CT-images from the treatment plan (left column) in order to position the patient accurately for treatment. Centers Around the World “On Board” with Varian IGRT Imager enables us to perform daily patient position verification and correct for any mismatches between the planned and the actual treatment position before every treatment. This gives us a sufficiently high degree of confidence to take on the most challenging cases.” Among such cases are situations in which a tumor has invaded the skull base and is encroaching on the brain or the visual pathway. “Daily imaging provides the quality assurance we need to deliver complex IMRT plans with the sharp dose gradients required for these extreme cases,” says Loo. Nancy Ellerbroek, MD, medical director for radiation oncology at Providence Holy Cross Cancer Center in Mission Hills, Calif., agrees. She treated a 17-year-old girl for a tumor of the nasopharynx. “Her tumor was close to her spinal cord and had invaded the base of her skull and some lymph nodes,” Ellerbroek says. “Prior forms of radiation therapy would have destroyed her salivary function. We also had to be concerned about neurological structures such as the brain stem and the optic nerve. We needed to be extremely accurate with our targeting.” Ellerbroek’s team treated the girl over a sevenweek period. Prior to every treatment, they used the On-Board Imager to make very fine adjustments to the patient’s position and line up the tumor so it fell squarely into the center of the treatment beam. The patient finished her treatment in October. “By the end of the treatment, her breathing problems had resolved, her headaches were gone, and no more signs of cancer were detected,” Ellerbroek says. “Her loss of salivary function was only slight - not the profound loss of function that we would have expected.” the end of “theBytreatment... no more signs of cancer were detected. - Nancy Ellerbroek, MD “ BREAST CANCER Conventional Fractionation In the United Kingdom, clinicians at Ipswich Hospital NHS Trust are studying the use of IGRT to improve the quality of conventionally fractionated breast cancer treatments. They use Varian’s On-Board Imager to generate daily radiographic kV X-ray images to visualize implanted gold marker seeds in the breast cavity following surgical excision of the tumor. The goal is to deliver radiation dose to the area at highest risk of recurrence. “It is tailored radiotherapy which some people have dubbed ‘risk adaptive radiotherapy,” says Andrew Poynter, cancer research lead at Ipswich Hospital. “Our initial experiences have been very encouraging.” LEFT | A color-wash representation of an IMRT plan for treating head and neck cancer shows how the radiation dose will be distributed in and around the tumor, with sparing of the spinal cord. RIGHT | On-Board Imager software performs a 3D-3D match comparing a cone-beam CT image with reference images from the treatment plan. It then calculates how to shift the patient in three dimensions to bring the tumor squarely into the isocenter. This work at Ipswich forms part of a pilot study led by Addenbrookes Hospital in Cambridge, which is examining the feasibility of using IGRT for post-lumpectomy breast cancer patients. The study will provide vital data for a national, multi-center trial to test riskadapted and partial breast radiotherapy treatment in patients at a high risk of local tumor recurrence. Accelerated Treatment of the Partial Breast At the Siteman Cancer Center at BarnesJewish Hospital in St. Louis, Simon Powell, MD, chairman of the department of radiation oncology at Washington University School of Medicine, offers select patients an accelerated five-day image-guided treatment option for breast cancer. Eligible patients include those with early-stage breast cancer that has not spread to the lymph nodes. “Patients love it because if they are eligible and they can have their treatment completed in a week, then they find it a lot more attractive than having six weeks of daily treatments,” he says. Powell and his clinical team use the OnBoard Imager in radiographic mode for daily target localization. For his accelerated partial breast treatments, Powell delivers 4 Gy over nine fractions, for a total dose of 36 Gy. He will compare the results with other dosing strategies, as part of a dose finding study. “We are currently completing an analysis of patients we treated at 36 Gy,” he says. “We are seeking what dose is biologically equivalent to the dose we are familiar with when we deliver 2 Gy each day over six weeks. It is still an open question.” According to Powell, the patients who receive the image-guided accelerated partial breast treatments do very well, in terms of adverse effects, compared with women who are treated according to more conventional fractionation schedules. “At worst, they might have a little bit of very transient skin rash. By the time you see them six weeks later, this has usually cleared up completely.” October 2007 | Varian Medical Systems 5 Centers Around the World “On Board” with Varian IGRT SPINAL LESIONS Prior to the advent of Varian’s IGRT solution, spinal metastases were generally treated with chemotherapy or long courses of fractionated radiotherapy. According to Patrick W. Elwood, MD, director of the Illinois Neurological Institute and professor of neurosurgery at the University of Illinois College of Medicine in Peoria, Varian’s Trilogy technology enables him to use either single or hypofractionated radiosurgery to shorten the treatment time and accelerate pain control while protecting the spinal cord from radiation effects. “The use of kV and cone-beam CT imaging has eliminated the need for fiducial marker placement, allowing this modality to be used more readily, thereby reducing the number of patients requiring extensive spinal reconstructive surgery or being left with unrelieved pain,” he says. Clinicians at Providence Hospital in Mobile, Ala., use Trilogy to deliver spinal treatments following a protocol that was pioneered by clinicians at Memorial-Sloan Kettering Cancer Center (MSKCC) in New York. The sensitivity of the spinal cord to radiation damage makes this an especially difficult area to treat, but IGRT smoothes the way and offers patients with spinal lesions a viable alternative to surgery. Robert Gilbert, MD, radiation oncologist, treated a 48-year-old man with lung cancer that had metastasized to the spine and brain. His brain lesion and one of two in the spine were successfully treated at M. D. Anderson Cancer Center in Houston, but subsequent PET and MR scans showed an active lesion in the spinal area. It was causing him a considerable amount of pain. In this case, Gilbert had to be especially precise because the spinal cord near the lesion had already received two-thirds of the tolerance dose. “We were able to use image-guided IMRT to keep the dose away from the spinal cord,” he says. “The Trilogy technology is perfect for just this kind of situation.” The On-Board Imager was used to detect a fiducial marker that had been placed into the targeted area under the periosteum. According to Gilbert, kV X-ray imaging is ideal for showing titanium or gold markers. “They show up beautifully,” he says. “The titanium markers are easier for the neurosurgeons to place. We would not be able to see them with megavoltage imagers.” Gilbert delivers these treatments in daily sessions over a five-day period. “At MSKCC, they are up to delivering 600 cGy per fraction, but they started out at a lower dose, and we are doing that as well,” he says. Gilbert is delivering 500 cGy per fraction and plans to escalate up to 550 if he sees good tolerance over a reasonable number of cases. “Today, if the original tumor is well-controlled using radiotherapy, chemotherapy, surgery or some combination of these, in many cases we can use radiosurgery or stereotactic radiotherapy to target the metastases and significantly prolong life,” Gilbert says. “We are seeing lung and brain cancer patients with metastatic disease living three LEFT | An image-guided radiosurgery treatment plan for a lumbar spinal metastasis. RIGHT | The nine-beam plan enables a high level of dose conformity with sharp dose fall off in the direction of the spinal cord. 6 Varian Medical Systems | October 2007 or four years and longer. That is because stereotactic approaches for delivering IMRT enable us to treat these lesions much more aggressively than we could have before.” MULTIPLE BRAIN LESIONS AND METASTATIC SPREAD Clinicians at the Virginia Commonwealth University Massey Cancer Center in Richmond, Va., were among the first in the world to control the spread of metastatic cancer using a Trilogy machine to deliver image-guided radiosurgery (IGRS). Theodore Chung, MD, PhD, radiation oncologist and associate professor at the VCU School of Medicine, used the technique to help a 47-year-old mother of four whose breast cancer had spread to her brain and liver. Chung and his team use the On-Board Imager along with Varian’s FramelessArray™ optical imaging system to pinpoint tumors and to continuously monitor and ensure that the patient remains properly positioned during treatment. The team also uses Varian’s RPM respiratory gating system to synchronize beam delivery with patients’ breathing patterns. For the patient with metastasized breast cancer, Chung and his team were able to treat all three brain lesions in a single course of treatment. The optical positioning system made it possible to avoid using a conventional head frame. “One lesion was close to the motor strip,” Chung says. “Too much dose to this area might have damaged her ability to move. The second lesion was close to the brain stem. By using the On-Board Imager to take radiographic X-rays, we were able to quickly line up bony anatomical landmarks each day and position the patient properly for her treatments.” To deal with the metastatic tumor in the patient’s liver, Chung and his team compensated for respiratory motion with a gated radiosurgery treatment. The Massey Cancer Center was one of the earliest adopters of Varian’s RPM system for targeting tumors that move during treatment due to the patient’s breathing. Centers Around the World “On Board” with Varian IGRT RECURRENCES Metastatic lesions, or cancer that has spread beyond the original tumor site to other organs, have been notoriously hard to treat, but Varian IGRT is making it possible to treat many forms of metastatic and recurrent disease, according to Michael Greenberg, MD, radiation oncologist at the Dales and Frances Hughes Cancer Center in East Stroudsberg, Pa. “As we get better and better at treating cancer, we are going to see more and more of these second malignancies. It is becoming a significant component of our practice,” he says. “In many cases, people receiving treatment at centers that do not have the latest IGRT technology are told they can’t receive any more radiation. IGRT makes it possible for us to treat patients successfully a second and even a third time with radiation,” Greenberg points out—sometimes even when the recurrence is at or near the site of the original tumor. For example, one of Greenberg’s patients, a man in his mid-60s who had been treated several years ago for esophageal cancer, developed bilateral pulmonary nodules with spread into the lymph nodes. This patient had a long cardiac history that precluded surgical intervention, and he was also not a candidate for chemotherapy. Greenberg was able to treat him with gated IGRT delivered over 30 fractions, however. “We did not hypofractionate in this case be- ABOVE | A treatment plan for simultaneously treating multiple brain metastases with a single isocenter. This type of treatment can be delivered in only 30 minutes using Varian’s Trilogy machine for image-guided radiosurgery. ABOVE | Michael Greenberg, MD, talks with a patient about image-guided radiotherapy for a metastatic lesion that appeared on her adrenal gland cause we thought normal tissue repair would be better with normal fractionation,” he says. “We were, of course, worried about overlapping the treatment fields with areas that had been previously irradiated. We used PET/CT to help us really localize the cancer, and fused those images with the treatment planning CT scan to make sure we were very tight on the targets.” Greenberg chose a sophisticated strategy for managing tumor motion in this case, because of the need to spare as much healthy lung tissue as possible. He used retrospective 4D CT scanning to generate the images for treatment planning, and created his plan using only images that corresponded to the relevant respiratory cycle phase. In the treatment room, the On-Board Imager was used to generate radiographic kV images to position the patient for treatment, as well as fluoroscopic images to check on the respiratory gating thresholds. “The goal was to prevent pneumonitis and pericarditis,” Greenberg says. “The ability to treat recurrances in the head, neck and prostate, along with metastatic lesions in the brain, liver, lungs and spine, is a major advantage for cancer centers that can offer patients the precision of Varian IGRT. PERSONALIZED CANCER CARE In highlighting the advantages of IGRT, Ellebroek points out that having the ability to generate images on a daily basis is immensely reassuring when she is delivering high doses of radiation to tumors close to critical structures in the body. “It allows me to deliver the powerful doses we know are better at eradicating tumors without cutting corners because we are afraid of getting too close to something crucial,” she says. “That means we can target tumors we would have considered untreatable just a year ago. I expect our tumor control rates will improve and our complication rates will be lower, when we have had a chance to study IGRT outcomes over a longer period of time. So far, our experience bears this out.” UPMC’s Dwight Heron agrees. “Technologies like these make it possible for us to adopt a truly personalized approach to cancer care,” he says. “Having a full integration of technological solutions that enable state-of-the-art, innovative treatment paradigms for a variety of cancers gives us the power to truly tailor cancer treatment for each and every patient.” October 2007 | Varian Medical Systems 7 DON’T TAKE SLOW FOR AN ANSWER. Let us bring you up to speed. 7 0 200/31 O –1 R 28 T / AS 10