LOMA LINDA UNIVERSITY MEDICAL CENTER PROTON TREATMENT AND THE CONTROL OF CANCER

Transcription

1 PROTON TREATMENT AND THE CONTROL OF CANCER AT LOMA LINDA UNIVERSITY MEDICAL CENTER

2 A NEW ERA BEGINS IN THE SEARCH "To MAKE MAN WHOLE" We stand at the threshold of an important advance in the control of cancer, in the relief of suffering, and in the betterment of life. Loma Linda University Medical Center (LLUMC) is leading the way to a new era in cancer care. A new form of radiation therapy offers reduced pain and suffering compared to current treatment methods, and unique medical advantages in controlling and managing cancer. The benefits of patient-dedicated particlebeam therapy will soon be available to persons with localized cancer... and the new LLUMC Proton Cancer Treatment Center will be a worldwide model for this new modality. LLUMC is implementing scientific advances from many of the world's leading national laboratories, universities and industries. The Proton Cancer Treatment Center results from the efforts of Loma Linda University and major collaborators, including Fermi National Accelerator Laboratory, Lawrence Berkeley Laboratory, Harvard Cyclotron Laboratory, the Paul Scherrer Institute, Science Applications International Corporation and the NBBJ Architectural Group. This collaboration has transformed physics concepts into medical care reality, resulting in another manifestation of Loma Linda University's fundamental mission: "to make man whole." As an expression of this mission, proton treatment is often called a "Beam of Hope It may provide a chance for patients to hope again, for their bodies to fight back again, and remain whole and healthy, and for families to unite in hope and effort. With the financial and technical help of Congress and the Department of Energy, and individual philanthropic efforts, the Proton Cancer Treatment Center will begin operation in ii LOMA LINDA UNIVERSITY LOMA LINDA UNIVERSITY MEDICAL CENTER LOMA LINDA, CALIFORNIA 92354

3 PROTON THERAPY: A NEW STANDARD OF Office of the President 414 4DAUVIVERSITY c_xedical 6EIVTER Loma Linda University Medical Center Proton Cancer Treatment Center Anders-on Street Rut Office Box 2000 Loma Linda, California (714) The new Proton Cancer Treatment Center is more than just a major advance for Loma Linda University Medical Center. The new center is also more than a breakthrough for medical treatment. As in all breakthroughs, it is even more than the sum total of its components which include billions of dollars of research and the talents of thousands of scientists and physicians over the past forty years. The center is in fact a new possibility for hope and healing, a potential treatment that can directly or indirectly affect every family in the United States, where today one in four people will be touched by cancer. The advantages of proton treatment of cancer near vital organs is well documented. Over the next few years, we intend to maximize the full potential of proton treatment, consistent with our mission, "To Make Man Whole." After two decades of research at LLUMC, the dedication of our staff and physicians, the extensive research at Harvard and Berkeley, the support of the U.S. Congress and generous individuals, we will soon open the world's first patient-dedicated Proton Cancer Treatment Center. Located in one of the most rapidly growing areas of our country, this is a center for the service of patients throughout the nation and from around the world. The Loma Linda effort represents one of the nation's largest and most expensive commitments to bringing the benefits of modern science and medicine to the healing of those who will confront cancer in their lifetime. We consider our commitment to be a direct support to every family in the nation. I hope that you will join with us in supporting and contributing to this international resource at Loma Linda University Medical Center. David B. Hinshaw, Sr., M.D. President PRECISION IN RADIATION TREATMENT Proton therapy differs greatly from today's conventional forms of radiation therapy. If given in sufficient doses, conventional irradiation controls many cancers. But, because of the physician's inability to conform the irradiation to the cancer in many cases, healthy tissues also receive a similar dose and are damaged. Consequently, a less-than-optimal dose is frequently used in order to reduce unacceptable damage to healthy tissues, and subsequent side effects. Cancer does not discriminate. It occurs in young and old, rich and poor, and in all races and ethnic backgrounds. In 1990, more than one million Americans will be diagnosed as having cancer. Within five years, about 600,000 of them may be dead. Some die because the disease spreads to distant vital organs, such as the lungs, liver or brain. Others, about 100,000 every year, die because the local tumor interferes with vital functions, such as breathing, eating, digestion and elimination of wastes. If the cancer is eradicated - at its place of origin, however, many deaths can be prevented. Proton treatment introduces greater selectivity in destroying cancer cells, reduces damage to surrounding healthy tissues, and greatly reduces the side effects traditionally associated with radiation treatment. Controlled dose distribution: key to control of tumors Protons deposit nearly all of their energy at the end of their desired path and cause very little lateral secondary scatter. Tissues upstream from the target receive only a small dose, and those to the sides of and behind the target receive virtually none. The energy given the protons by the accelerator controls their depth of penetration. Proton beams, therefore, deposit nearly all of their energy on target. Physicists call the point of energy release the Bragg peak. Such precision allows the radiation oncologist to increase the dose to the tumor, while reducing the dose to surrounding healthy tissue. The result is higher tumor-destroying doses and fewer side effects than can be accomplished with conventional radiation therapy. This is especially important when the tumor is close to vital sensitive organs. As we approach the 21st century, physicians will learn of the results of the new treatment at Loma Relative Dose Linda, and other proton cancer therapy centers are expected to serve patients around the world. In the meantime, the pioneering work at Loma Linda will be available to patients everywhere Depth in Tissue (cm) Comparison on depth dose distribution for X-, 'Y-ray, and electron beams with distribution of a proton beam. This graph compares the energy-loss characteristics (dose) of various types of radiation used in the treatment of cancer. (Adapted from a publication of the PARMS facility, University of Tsukuba, Tsukuba, Japan.) 4 A Seventh-day Adventist Institution 5

4 Bragg peak concentrates dose in the tumor, decreasing damage to healthy tissue A single 18 MeV x-ray beam entering from the front. The central circle represents the prostate gland. The irregular structure outlined in white below the prostate gland represents the rectum. A single x-ray beam entering from above deposits most of its energy within the small bowel and bladder before reaching the tumor. Proton therapy is a new modality in cancer treatment offering much greater precision than conventional radiation therapy. This precision enables physicians to deliver higher, more effective doses to target volumes. _ The Bragg peak for monoenergetic proton beams is only a few millimeters wide; this is significantly smaller than most radiation therapy volumes. However, the peak can be spread to any desired width by energy modulation. The LLUMC accelerator, a type known as a synchrotron, has continuously variable energy corresponding to a tissue range variation from 3 mm. to 38 cm., the full depth of the body of a large person. Thus, by varying the energy, the Bragg peak can be precisely shaped to deliver homogeneous doses of radiation to irregularly-shaped threedimensional tumors. Ocular melanomas The benefits of a concentrated dose can be seen in the treatment of tumors inside the eye, such as ocular melanomas. Proton treatment has become a very effective and desirable treatment for ocular melanomas because it spares the sensitive tissue of the eye and usually preserves the patient's vision. Proton treatment is successful in over 95 percent of these cases. Current conventional treatment of ocular melanomas usually involves removal of the patient's eye, with resulting disfigurement and loss of vision. Lateral beam using 18 MeV x-ray beam deposits maximum energy within the bony structure of the hips. Proton beams from the sides deposit maximum energy within the prostate tumor, minimizing radiation to normal structures. A combination of four 18 MeV x-ray beams deposits maximum dose within the region of the prostate. Note the large volume of normal tissue receiving greater than 40% of tumor dose. Three proton beams confine dose greater than 40% to the region of the tumor, with minimal radiation to surrounding normal tissues. This allows the potential for increasing the dose of radiation to the tumor. A proton beam deposits its maximum energy within the tumor in the prostate gland, minimizing the dose to the small bowel and bladder. 6

5 NEW IMAGING TECHNOLOGY: A NECESSARY FOUNDATION FOR PROTON THERAPY PHYSICS RESEARCH: INSTRUMENTAL IN MEDICAL PROGRESS... FROM VISION TO REALITY Treatment of malignant diseases with highenergy ion beams has been confined until this time to particular disease sites, such as the head. Until recently, diagnostic imaging was not precise enough to define target volumes that would enable oncologists to fully exploit proton beams. The availability and widespread use of devices An MRI scan of a child's head and neck revealing a central brain tumor, outlined in green. such as Computed Tomography (CT scanners), Magnetic Resonance Imaging (MRI), and others, have now made it possible for physicians to define tumor volumes with such accuracy that threedimensional localization of radiation effects is not only practical, but is mandated for future treatment - of many cancer patients. A cross-section of the same patient showing the distribution of radiation from two proton beams directed at the tumor volume. Note how well the radiation is confined to the tumor. In actual treatment, a third beam would further confine the radiation to the tumor. Proton and heavy-ion acclerators, all originally built for physics research, have been used for medical therapy for more than 30 years. They have been somewhat limited because the beam energies are not necessarily correct for therapy and because the energy cannot be varied easily. In spite of the limitations, these accelerators have been highly successful in the control of tumors of the head and neck, eye melanomas, prostate and pelvic tumors, and non-cancerous diseases such as Cushing's disease, arteriouvenous malformations, and others. Ernest Lawrence, inventor of the first modern accelerator, and his brother John Lawrence, a physician, treated a few cancer patients (including their mother) with neutrons in the 1930s. Robert Wilson, who had been a Ph.D. student of Ernest Lawrence's, first proposed the use of protons in He made this treatment one of the goals of the cyclotron he was then building at Harvard. This accelerator was used to treat patients beginning in 1959, and has treated more patients than any other accelerator. Many pioneering innovations have been introduced by the physicians and physicists at Harvard Cyclotron Laboratory and Massachusetts General Hospital. Work has also continued at Lawrence Berkeley Laboratory, University of California at Berkeley. Here the emphasis has been on ions heavier than protons. Heavier-ion beams have some advantages and disadvantages in dose distribution, compared to protons. In addition, heavier-ion accelerators are substantially larger and more costly to build than proton accelerators, since the energy per nucleon of the heavy-ion beams must be the same as the proton energy for equal penetration in tissue. Proton therapy has also been used in Japan, Sweden, Switzerland, and at three laboratories in the Soviet Union, again with good results. All these accelerators were also originally built for scientific research. Clinical work at Massachusetts General Hospital and at the University of California at Berkeley has been supported by the National Institutes of Health. Photographs of a patient's tongue before and six months after treatment with proton beams by Dr. Toshio Kitagawa. The treatment took place at the Particle Radiation Medical Science Center (PARMS) of the University of Tsukuba in Japan, using a proton accelerator originally built for research in particle physics. An example of pelvic tumor with irregular-shaped volume treated by three proton beams. Note how high-dose region can be shaped to conform to an irregular-shaped tumor. 8

6 A NEW TOOL FOR CONTROLLING CANCER The Loma Linda University Medical Center Proton Cancer Treat- design and build, and contains the world's smallest synchrotron ment Center is the first in the world to offer proton therapy, built by Fermi National Accelerator Laboratory. It is as large as designed to treat cancerous tumors without harming surrounding some hospitals, can serve up to 100 patients in a 10-hour day, healthy tissue. The center cost $40 million, took four years to and is a model for worldwide training and research. HOW A PROTON BEAM WORKS The beam enters the body at a low absorption rate and increases in intensity at a specific point, called the Bragg peak. A series of peaks are focused on the tumor, giving it the highest concentration of radiation, killing the cells of the tumor. Not only is the dose of radiation to normal tissue sharply reduced, compared to conventional radiation therapy, but the energy of the proton beam completely dissipates within the tumor, causing no damage to normal tissues beyond the tumor. THE GANTRY Three gantries resembling giant ferris wheels can rotate around the patient and direct the proton beam to a precise point. Each gantry weighs about 90 tons and stands three stories tall. The 3 5-foot-diameter gantries support the bending and focusing magnets to direct the beam, and have a counterweight for extra radiation shielding. Gantry 1 Gantry 2 Gantry 3 THE INJECTOR Protons are stripped out of the nucleus of hydrogen atoms and sent to the accelerator. STATIONARY BEAM The stationary beam has two branches, one for irradiating eye tumors and the other for central nervous system tumors. 10 Steel-reinforced concrete walls are up to 15 feet thick. SYNCHROTRON (ACCELERATOR) The synchrotron is a ring of magnets, about 20 feet in diameter, through which protons circulate in a vacuum tube. As the magnetic field in the ring is increased, the energy of the protons is also increased. When the magnetic field reaches the value corresponding to a prescribed beam energy, the field is held constant while protons are slowly extracted from the ring. The system accelerates protons to a minimum energy (70 million electron volts) in onequarter second and to maximum energy (250 million electron volts) in one-half second. BEAM TRANSPORT SYSTEM The Beam Transport System carries the beam from the accelerator to one of four treatment rooms. This system consists of eeveral bending and focusing magnets which guye the beam around corners and focus it to the desired spot size and location within the vacuum tube. The system monitors the size, position, and intensity of the beam at many points. Variations from the prescribed parameters send messages through the computer network to adjust the beam or to trip interlocks which automatically shut it off. WHAT THE PATIENT SEES The patient rests on a couch or sits in a chair, as appropriate for treatment. Alignment and verification of the patient to the beam, controlled from a room just outside the treatment room, will take most of the time; actual beam time takes less than a minute. Most patients will be able to return to work or other activities immediately after the procedure.

7 Robert Wilson, Ph.D., creator of proton therapy; founder of Fermilab FERMILAB: ITS ROLE IN PROTON THERAPY DEVELOPMENT IN THE U. S. Robert Wilson founded Fermilab and led it through its first decade. He maintained his longstanding interest in proton therapy, and in the early 1970s, he and some of his colleagues proposed to use the Fermilab linear accelerator for therapy when it was not in use as an injector. But, the ability to use the localizing capability of protons depends on knowing the location of the tumor. The technology to perform this localization was not fully developed at that time, and physicians collaborating with Fermilab urged the scientists to produce neutrons with the proton beam, to enable them to treat patients with those particles. Neutrons are somewhat more efficient than pro- tons or electrons at killing cells, but do not have protons' advantages in localizing the dose. The Fermilab Neutron Therapy Facility has been in operation for more than twelve years and has treated more than 1,800 patients. In the intervening years, proton therapy has proceeded at Harvard, and CT scanning and MRI have come to fruition. With their use, it is possible to take full advantage of the tight control of the irradiated site that can be done with protons. It is now advantageous to build an accelerator and facility specifically for the treatment of disease with proton beams in a hospital setting. In January 1985, a group interested in studying the design of potential proton accelerators, facilities, and clinical trials met at Fermilab in Batavia, Illinois, for the first in a series of meetings. In these meetings, the group, which came to call itself the Proton Therapy Cooperative Group (PTCOG), proposed and discussed a variety of machine designs and beam-delivery systems. One outgrowth of the PTCOG meetings was an agreement.between Loma Linda University and Fermilab, whereby Fermilab designed and fabricated a 70 to 250 MeV proton synchrotron and assisted in the design and procurement of a beam transport and delivery system for installation at Loma Linda University Medical Center. Fermilab is owned by the United States Department of Energy and operated by Universities Research Association, Inc. Leon M. Lederman, Ph.D. Former director, Fermilab The laboratory is located on 6,800 acres, about five miles east of Batavia, Illinois. The four-mile-in-circumference main accelerator at Fermilab is located in a tunnel 20 feet below the ground. John Peoples, Jr., Ph.D. Director, Fermilab Robert Wilson Hall, the laboratory building that is the focus of Fermilab. The Loma Linda synchrotron was designed and fabricated at Fermilab

8 The Proton Cancer Treatment Center is designed for patient and family support, as well as treatment. THE NEW ERA BEGINS: LLUMC's PROTON CANCER TREATMENT CENTER For the scientists, physicians, administrators, and staff of LLUMC, two decades of research, leadership, commitment, and the intention "to make man whole" led to the soon-to-be-opened center. The new center is designed for patient and family support, as well as treatment. A major goal is that patients and their families be as cornfortable as possible. The center will be primarily an outpatient facility. Although inpatients will be treated, it is anticipated that most patients will be treated on an outpatient basis. Further, it is anticipated that most patients will need fewer visits than conventional radiation therapy requires, and that the individual treatments will be less threatening because of reduced side effects. Decreasing the fear of treatment is one of the anticipated benefits, and the entire center is designed to create a pleasant atmosphere. The accelerator in action The LLUMC proton accelerator is a synchrotron, chosen because it can be designed to deliver enough beam energy to reach the deepest tumors in the most-obese patients. The beam energy of the synchrotron can be easily varied, allowing for the irregular volumes needed to treat most cancers. The LLUMC synchrotron is a ring of magnets, through which protons circulate in a vacuum tube. As the magnetic field in the ring is linearly increased, the velocity (energy) of the protons is synchronously increased. The protons are accelerated at a rate that keeps them precisely in the center of the vacuum tube. When the magnetic field reaches the value corresponding to a prescribed beam energy, the field is held constant while protons are slowly extracted from the ring and delivered to the patient. One can vary the beam energy by terminating the accelerating cycle at the magnetic field that corresponds to the energy needed for treatment. The system accelerates protons to minimum energy (70 million electron volts) in one-quarter second and to maximum energy (250 million electron volts) in one-half second. The synchrotron has an injection system, consisting of an ion source, a small linear accelerator, and guidance and focusing magnets. The injection system supplies protons to the synchrotron, giving the particles the necessary initial characteristics to be accelerated in the synchrotron ring. The radiation oncologist and physicist develop a treatment plan using a computer-assisted planning system. The completed plan is taken to the control computers, where the data are entered. This information drives most components of the system. Then, the computer is instructed to extract the beam from the synchrotron for delivery to the target within the patient. The Beam Transport System carries the beam from the accelerator to one of four treatment rooms. This system consists of several bending and focusing magnets, which guide the beam around corners and focus it to the desired spot size and location within the vacuum tube. The system monitors the size, position, and intensity of the beam at many points. Variations from the prescribed parameters send messages through the computer network, to adjust the beam or to trip interlocks which automatically shut it off. The system also includes a beam dump, which safely discards unused protons. The system transports the beam to five different rooms, although only one will use the beam at a given time. Three of the rooms have a gantry system. Each gantry is 35 feet in diameter, weighs about 90 tons, supports bending and focusing magnets to direct the beam, and has a counterweight for extra radiation shielding. The gantry can rotate the beam around the patient, allowing one to treat several portals. One treatment room has a stationary beam with two branches, one for irradiating eye tumors and the other for central nervous system tumors. The fifth room, used for beam calibration and basic research, also features a stationary beam. Each treatment room has a Beam Guidance System that directs the treatment beam. The guidance system continuously monitors the beam as it sweeps over the treatment volume. Field sizes as large as 40 x 40 cm. will be possible by scanning the beam back and forth. The Beam Guidance System positions the Bragg peak to conform to the size and shape of a tumor. A host computer will control the accelerator and the Beam Transport System. A second computer, located in each treatment room, will control the Beam Guidance System and other treatment facilities. This computer will verify patient identification, set operational parameters for each patient's treatment plan, and direct the host computer to deliver a specified beam. These tasks have been well-tested and executed at Loma Linda and at Fermilab

9 WORLD'S FIRST HOSPITAL-BASED PROTON AN INTERNATIONAL CANCER TREATMENT CENTER RESOURCE FOR THE Lorna Linda University Medical Center's facility, opening in 1990, will be the model of therapy utilizing a dedicated variable-energy proton synchrotron to serve patients. At Loma Linda, the synchrotron will supply beams to several treatment rooms. The accelerator was built at Fermi National Accelerator Laboratory in Illinois. Final testing was completed in fall of 1989, and assembly is now underway at Loma Linda in a three-story underground treatment facility designed by The NBBJ Group. The system to guide the beam to its target was developed by scientists at Loma Linda University Radiation Research Laboratories (LLURRL), Lawrence Berkeley Laboratory (LBL), and Harvard Cyclotron Laboratory (HCL). The principal component of the guidance system is a raster scanner, a device which uses a magnetic field to conform the path of the beam to the shape and size of a tumor. The center will serve up to 2,000 patients every month. For the patients and their families, the facility will offer the opportunity for better cancer therapy, given with precision, compassion and dignity. For some tumors, treatment times will be shorter. LLUMC anticipates that patients will be less troubled by the side effects associated with conventional treatment, and less fearful. The new center leads the way for development of additional proton therapy facilities throughout the world. In addition to the technological innovations at the center, LLUMC physicians, working with scientists at LBL, HCL, and around the world, will generate data on the value of proton therapy for disease control. This data will be available worldwide. The Loma Linda Proton Cancer Treatment Center will be an international resource for research and learning about proton therapy. Topics which will be investigated include: clinical research on proton beams for malignant tumors and some benign diseases in sites throughout the body; radiobiological studies; physics and engineering studies on the accelerator; and beam delivery combining proton therapy with other treatment modalities. Successful technology transfer occurring in this project is a landmark demonstration of basic science applied to the betterment of all. David B. Hinshaw, Sr., M.D. President, LLUMC James M. Slater, M.D., Director Radiation Sciences, LLUMC REGION AND NATION The center will serve Loma Linda University Medical Center and its affiliated hospitals, including a Veterans Administration hospital, two general hospitals and two community hospitals. Patient referrals to the Proton Cancer Treatment Center will come from Southern California, from around the nation, and from throughout the world. It is anticipated that, in the 1990s, LLUMC will be one of the centers on the leading edge of care and healing. Patients arrive daily at one of Loma Linda University Medical Center's two heliports. This resource will also be available to patients coming to the Proton Cancer Treatment Center. 4" tiq I I Fri F; r"," - "-r I The Loma Linda University Medical Center, Loma Linda, California 16 17

10 LOMA LINDA UNIVERSITY MEDICAL CENTER Loma Linda University Medical Center's fundamental commitment to proton therapy springs from the mission of the physicians, scientists, administrators, and staff to serve all people. The Proton Cancer Treatment Center is a demonstration of the continuing commitment "to make man whole." As such, the new center is one of the largest financial commitments the Medical Center has ever made. We expect our program to go far beyond improved cancer control. In the spirit of our mission, we will provide patients and their families with physical, mental, and spiritual support, assur- ing them the care, hope, and love they need. Loma Linda University Medical Center is the principal hospital center in the fastest-growing and largest county in the United States. The institutioris medical school is the second-largest private medical school in California. Loma Linda University Medical Center serves all mankind; it has outreach programs to nations throughout the world. The Medical Center's reason for being is characterized by the Good Samaritan sculpture at the forefront of the campus, symbolizing Seventh-day Adventists' attitudes toward health and the mission of the Medical Center. The text in this presentation is condensed and extracted from two principal sources. The first is a document prepared for publication in the International Journal of Radiation Ona9logy by James M. Slater, M.D., Daniel W. Miller, Ph.D., and John 0. Archambeau, M.D., of Loma Linda University, Loma Linda, California. This is supplemented by material written by Philip Livdahl and Francis Cole of the Fermi National Accelerator Laboratory in Batavia, Illinois. Photographs were supplied by: Loma Linda University Medical Center, Fermilab, Massachusetts General Hospital, and PARMS. 18

11 A A A Loma Linda:Universt Medical Center is:the firsrin the wolf 4 a,, proton' therapy system -designed for patietire'are. 'Proton' therapyresiilts from over 40 `years.,of high-energypaysirsyrsearchvith charged Particlis;Vnd has already success- treated:8xx; Patiengin various testing: laboratories..proton therapy ka:s;hee ;called the 0:N:essential; example of technology,. spin off from abstratt basit':relearch to humanitarian:,mse,,,7 by D>r eoni, Lederman Nobel Laureate for Physics in 19B8.1 Loma: Linda University Medical :Center,. researched 0:ton therapy,for-20 years prior to opening the Prowl, Cfincer;,,Triaimerit:;Gen tin Benefits ofproton:freatrnent are: 1 ',Signif;canify,reduced.side efects: Powerful la'nd, pnyise treatment; with a uniquegbiljotospgre i)itatorians. -New hope and promise for controlling cancer. The 'LLUAIC Proton Cancer Treatment Center- cost.40 million,. too:klaur, yeeirsioidpign and build, contains a variablereneri;:synchroti-onkilit b Ferini,Nitional:Iccelerator Etiboratory:a1:S. DepaetMelit of Energy), and received :a signifieort,trant fr m Congress / U.S. Department of Erieitt,to:S.UPP4od the synchrotron develppment. l_44 The:LLOMe-Proton Cancer Treatmen4Ceit&is as large as some hospitals, can,se:rve;up f;to:100' patients a 10-hour day, has four` proton treatment rooms,- and = in addition to the treatment services 4is a modelifor worldwide training and research, The Proton. cancer treatment Center Was bu lt. by LLUMC as : A eirthet-, 'eaepressiorl of our commitment "to make man whole." COMA LINDA UNIVERSITY LOMA LINDA UNIVERSITY Lorna Linda University 4'' Loma,. Linda, Uilier6ty N46Sdic[ Cen t r VIEDICAI, CENTER (7:1!) ' (711)

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