PROMISE& PROGRESS

THE SIDNEY KIMMEL COMPREHENSIVE CANCER CENTER AT JOHNS HOPKINS

Proton Therapy Is Here A New Standard of Care

2020/2021 & Care. P P Collaboration. THE SIDNEY KIMMEL COMPREHENSIVE CANCER CENTER AT Innovation. JOHNS HOPKINS

Promise & Progress PROTON THERAPY IS HERE. The new have the most advanced pencil beam, is published by Johns Hopkins National Proton Center at which paints tumors with cancer cell- The Sidney Kimmel Comprehensive Cancer Center Sibley Memorial Hospital is built upon a killing energy layer by layer, staying within at Johns Hopkins long and rich tradition of excellence in the boundaries of the tumor. The Office of Public Affairs Baltimore, Maryland radiation oncology, bringing nearly a beam adjusts to differences throughout a 410-955-1287 half-century of cancer discovery and tumor to provide the right amount of William G. Nelson, M.D., Ph.D. clinical progress to proton therapy. energy to every different area of the tumor. Director One size doesn’t fit all. Every patient, Amy Mone every cancer, is different, so we are Director of Public Affairs ushering in the most advanced tumor Valerie Matthews Mehl monitoring that makes the already safe Editor and Sr. Writer [email protected] and targeted pencil beam patient-specific Megan Mattis and even more tumor-specific. Advanced Photography Assistant imaging and sophisticated data mining Howard Korn, Joe Rubino, Tim Bloomquist will make complex comparisons of Feature Photography photon and proton therapies to ensure For additional copies of this each patient receives the therapy that is publication or further information best suited to his or her unique cancer. about the Kimmel Cancer Center, We have the world’s leading experts please call 410-955-1287 across all disciplines and specialties or email [email protected]. working in collaboration. This includes MSK Partners, Inc. a collaboration with Children’s National Design and Production Hospital to create one of the largest pediatric radiation oncology programs in the country. Few other centers can claim Connecting this level of expertise. We know cancer Promise to Progress It’s striking that this technology has and proton therapy. That is the Johns On the Web been around for more than 40 years but Hopkins difference. There are centers that CONNECT WITH US HOPKINSCANCER.ORG has never really been tested in the can deliver proton therapy, and then there research setting. This is what sets us apart are centers like ours that combine the FACEBOOK.COM/HOPKINSKIMMEL from other centers. We ask the tough highest level of cancer care with YOUTUBE.COM/HOPKINSKIMMEL questions because we are prepared to go scientific innovation to make sure the after the answers. With a dedicated cancer medicine we deliver is the best TWITTER.COM/HOPKINSKIMMEL proton research laboratory, our experts medicine for each patient. Our new INSTAGRAM.COM/HOPKINSKIMMEL are ready to do the hard work and gather National Proton Center enhances our mis- the much-needed evidence to guide when sion of curing cancer and changing lives. PODCASTS: HOPKINSKIMMEL.LIBSYN.COM and how proton therapy is best used. CANCER-MATTERS.BLOGS.HOPKINSMEDICINE.ORG We waited until the technology was OUR-CANCER.BLOGS.HOPKINSMEDICINE.ORG right to bring proton therapy to Johns William G. Nelson, M.D., Ph.D. Hopkins, and when we did, we made Marion I. Knott Professor and Director FOR APPOINTMENTS AND OTHER INFORMATION, CALL 410-955-5222 it better, customizing it with our own The Sidney Kimmel Comprehensive inventions. Our proton therapy center will Cancer Center at Johns Hopkins ©2019 The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins 2 PROMISE & PROGRESS

Proton Therapy Is Here Johns Hopkins excellence is setting a new standard of care

Technology without advanced and compassionate care is The translational ingenuity that merges science alone. But technology in an environment of compas- laboratory discovery with clinical care thrives in the Kimmel Cancer Center. It sionate care, discovery and multispecialty collaboration was engaged throughout the planning focused on improving the lives of patients is cancer medicine. and construction of our proton center. As This is the hallmark of Johns Hopkins and the Kimmel Cancer a result, it is one of the most comprehen- sive in the world, one of the very few sep- Center, where innovation that exceeds the standard is the arate, dedicated rooms for research, norm. The result is an unsurpassed level of expertise in radiation pediatric patient care and adult patient oncology, molecular radiation sciences, physics, surgical care. Proton therapy has raised many oncology, medical oncology, cancer biology, engineering, questions about for whom and how it is best used. Our experts are answering quantitative sciences and more that Johns Hopkins Medicine those questions. They are providing the brings to proton therapy. This level of knowledge and “why” and “when” of proton therapy. multispecialty collaboration are fundamentally what set the Despite commercial advertising to the contrary, proton therapy is not new, and Johns Hopkins National Proton Center apart from most other the science is far from settled. “Although proton centers across the U.S. Expertise matters because the it has been around for a long time, it is real value of proton therapy is in the specialists who develop very much in its infancy in terms of ex- and use it. ploration and potential,” says Akila Viswanathan, interim director of the Department of Radiation Oncology and Proton therapy may be a rare commodity, cancer discovery and clinical progress to Molecular Radiation Sciences. with less than 40 centers in the U.S., but proton therapy.” this level of expertise is even rarer. The COLLABORATION Kimmel Cancer Center is among the very Although this technology provides new few that will combine cancer treatment opportunity to move cancer science and Proton therapy has excellence across all disciplines with medicine forward, not all proton ther- proton therapy excellence. apy is created equal. We are not simply raised many questions users and deliverers of proton therapy. about for whom and “Patients and families need the team that Our scientists are also inventors, knows the most about the tumor. You driving, testing and improving the how it is best used. need to know cancer, not just proton technology to create a proton facility Our experts are helping therapy. That is a differentiator for us,” unlike any other. Building upon a says William Nelson, Director of the lengthy history and strong foundation answer those questions. Kimmel Cancer Center. “We bring the of pioneering discoveries in radiation They are providing the full complement of Johns Hopkins therapy, this center has the technology expertise, spanning programs and to deliver the most advanced and “why” and “when” of departments, and nearly a half-century of patient-centered care. proton therapy. THE SIDNEY KIMMEL COMPREHENSIVE CANCER CENTER at JOHNS HOPKINS 3

The Synchrotron HOW IT WORKS A synchrotron is a type of particle accelerator used to accelerate protons for Inside Our Proton use in proton therapy. It is 26 feet in diameter and Therapy Center composed of a ring of small magnets. Protons are The proton is small, but it takes big injected into the ring and begin traveling around machinery to generate and move these the ring at great speeds, subatomic particles for treatment. about 10 million times per second. Put another way, the speed of the protons is so fast, it could circle around the earth five times in one second. It is advanced technology over earlier generations of proton therapy because it can produce beams of a Gantries wide range of energies and Protons travel down reduces the risk of unnec- magnetic devices into essary and unwanted the treatment rooms. radiation to the patient. A 360-degree, rotating, 30-foot-diameter iron framework, called a gantry, controls the speed and direction of protons. It allows radiation oncologists to Pencil Beam Scanning direct the beam at any This new technology funnels angle and deliver the the protons into a narrow proton beam with beam—just a pencil tip’s pinpoint accuracy Respiratory Gating to a patient’s cancer. width—coming out of the The slightest motion proton therapy machine can cause tumors hundreds of times per Our center has four of to move. Our proton these, with one gantry second, scanning the tumor therapy beam tracks back and forth and up and dedicated exclusively directly to the tumor, for pediatric patients down, just to the edges of stopping if the tumor the tumor, to paint it layer by and another for much- shifts with the patient’s needed research. layer with the cancer-killing breathing and starting proton beam. Our advanced up again when the technology is intensity mod- beam and tumor are ulated, making it possible aligned. to deliver varying degrees of energy targeted to the specific composition of each area of the tumor.

On-Board Imaging Ours will be among the first to have on-board imaging. Plans for a CT Couch, invented by medical physics Director John Wong in collaboration with Hitachi, will provide a built-in CT scanner that merges images of the cancer taken during treatment planning with ones taken the day of treatment to verify that the tumor being treated has not changed or moved. It facilitates precision treatment within one-tenth of 1 millimeter accuracy. 4 PROMISE & PROGRESS

As a result, what truly is new in proton problem, Wong invented the Small Ani- and where can we reduce toxicity? therapy is what the Johns Hopkins mal Radiation Research Platform Where are we not getting such benefit National Proton Center brings: the labo- (SARRP), a miniaturized version of the and can let go? This is an area that is ratory and clinical research to make it machines used to treat humans that is for lacking, and our center can begin to get better and to advance its use as a tool of animal research and potentially other to the answers.” The Johns Hopkins precision medicine. Our proton center is laboratory models. “SARRP provides a National Proton Center will be solving among a select few academic centers in realistic model to study in the laboratory these unknowns and leading future the country—and the only in the region— the radiation treatment we give to progress, says Deville. doing research to determine in which patients, and this is critical to quantify- situations this type of radiation treat- ing the benefits of one type of radiation Radiation oncologist and gastrointestinal ment is the best option. therapy over another and to finding the cancer expert Jeffrey Meyer was drawn safest and most effective way to treat to Johns Hopkins for the same reason. INNOVATION patients,” he says. Meyer completed a fellowship in proton Radiation treatment, therapy before coming to the Kimmel Lack of research has been one of the Cancer Center and says that the Johns in all of its forms, most common criticisms of proton ther- Hopkins National Pro- is essentially a form apy. Although most experts agree that its ton Center is one of the ability to spare healthy cells by zeroing few addressing compli- of minimally invasive directly in on and stopping at the end of cations associated with surgery that replaces tumors makes proton therapy the radia- proton therapy, such as tion treatment of choice for pediatric organ movement and scalpels with precisely and adult patients with tumors in the MEYER sensitivity to density targeted radiation to brain or on or near the spinal cord, de- in organs. All of these questions and finitive research studies are lacking. concerns can be mitigated with get to cancers. Wong and collaborators are currently research, he says. adapting SARRP to study proton therapy. Proton therapy does not replace other One room in the proton center is outfit- “There are always going to be new tech- forms of radiation therapy. “We do well ted specifically for research and will be nologies. Expertise and the willingness to with all forms of radiation therapy, and dedicated to the specific cellular, physics do research to know how to use it are that’s something most other proton and animal studies needed to refine and critical,” Meyer says. “It’s a great technol- centers do not offer. That’s important define who is best treated with proton ogy we want to take advantage of, but we because not every patient will need therapy. have to be smart about how we use it.” proton therapy,” says Viswanathan. “What Johns Hopkins does so well is Other proton experts, including “Too much information is marketing research to improve patient care,” says Matthew Ladra, a pediatric cancer driven and not fact driven. Claims of Theodore DeWeese, Vice Dean for Clin- specialist who directed a proton center clinical benefit are made with no scien- ical Affairs and former in Tennessee, and Jen Holt, a nurse from tific evidence to back them up. There is director of the Depart- the same center, came to Johns Hopkins a lot we still do not know biologically,” ment of Radiation On- and the Kimmel Cancer Center because says John Wong, director of medical cology and Molecular of the combined excellence in research physics. “At Johns Hopkins, we do it Radiation Sciences. and patient care. right.” “We are one of the only

DEWEESE proton centers that has “There are many aspects we still don’t Radiation treatment, in all of its forms, is a whole room dedicated to thiskind of know and a lot of essentially a form of minimally invasive research.” research opportunities. surgery that replaces scalpels with That’s something we precisely targeted radiation to get to can- Proton therapy expert Curtiland Deville bring to the table, with cers, Wong explains. “The main reason says it is the reason he came to Johns the goal to figure it all there is no scientific evidence to support Hopkins. “I wanted to be in an academic out and bridge these

many of the claims of benefit is that center to be at the forefront of solving LAIHO gaps in knowledge,” there was no way to do research. There issues and questions about proton ther- says Marikki Laiho, director of the Divi- was no laboratory counterpart for what apy: What are the best indications for sion of Molecular Radiation Sciences. we do in the clinic,” he says. To solve that proton? Where can we increase benefit, COLLABORATION THE SIDNEY KIMMEL COMPREHENSIVE CANCER CENTER at JOHNS HOPKINS 5 At left, John Wong, M.D. director of medical physics. The Johns Hopkins National Proton Center build upon a lengthy history of pioneering discoveries in radiation therapy and offers the technology to deliver the most advanced and patient-centered care.

INNOVATION Heng Li, Ph.D., Chief Proton Physicist, helps bring patients the most advanced radiation therapy technologies, latest techniques and innovative treatments. 6 PROMISE & PROGRESS INNOVATION Akila Viswanathan, M.D., M.P.H., Interim Director of Radiation Oncology and Molecular Radiation Sciences, says although proton therapy has been around for a long time, it is very much in its infancy in terms of explo- ration and potential. What truly is new is the research and multispecialty collaboration the Johns Hopkins National Proton Center brings.

“We do well with all forms of radiation therapy, and that’s something most other proton centers don’t offer. That’s important because not every patient will need proton therapy.” THE SIDNEY KIMMEL COMPREHENSIVE CANCER CENTER at JOHNS HOPKINS 7

Photons and Protons One key difference between X-ray or DeWeese says photons and protons both Radiation oncology is unique in that it is photon radiation therapy and proton have their place in radiation therapy, the only specialty that makes its own therapy is already known. It goes to the and that’s why advanced knowledge of medicine. Radiation treatments deliv- very core of why proton therapy is bene- the field is so important. One area, he ered by machines essentially come in one ficial. It’s not that it kills cancer better; says, where the benefit has clearly been of two forms: photons or protons. Al- it’s that it damages normal cells less. demonstrated is pediatric patients and though every radiation oncology expert Photons pass through the cancer and out recognizes that photon therapy and the other side, so on this exit, they hit INNOVATION proton therapy are different, no one has normal cells and tissue. Proton therapy, As protons travel studied them at the level proposed by on the other hand, stops at the tumor. our experts. There is no exit dose. “Conventional through the body, photon radiation therapy and proton most of the energy "We will be able to leverage our extraor- therapy cure tumors at the same rate,” dinary talent in order to advance the explains Viswanathan. “The side effects is reserved and field," says Viswanathan. they can cause are similar, but with proton, less dose goes to normal cells, released where the Long-term research data made possible and that’s the benefit.” protons stop—in through Wong’s SARRP technology make the tumor. Photons it possible to begin comparative pho- ton/proton studies almost immediately. BRAGG PEAK release energy along As protons travel through the body, the entire path they “This will give never-before-seen insights most of the energy is reserved and released into the actual biologic effects of proton,” where the protons travel. she says. stop—in the tumor.

Photons are a higher-energy version of tumors in the brain, spine and when the the same X-rays used for diagnostic im- cancer is located close to vital organs, aging. These high-energy X-rays can be like the heart. Head and neck cancers, pointed at a part of the body where a tumors located at the base of the skull cancer is located and, through a series of where nerves come out, breast cancers interactions inside of the body, break the near the heart, lung cancers in the DNA inside the cancer cell, rendering it middle of chest or near the esophagus, unable to repair or copy itself. As a certain pancreas and abdominal result, the cancer cell dies. What Viswanathan describes is technically tumors—essentially any cancer located known as the Bragg peak. As protons in or around complicated anatomy that Proton therapy is called heavy ion ther- travel through the body, most of the needs to be shielded from radiation— apy. It essentially kills cancer in the same energy is reserved and released where may be better suited for proton therapy. way—breaking the DNA—but it uses the protons stop—in the tumor. Photons When combined with lumpectomy, pro- charged particles directly rather than release energy along the entire path they ton therapy could potentially improve X-rays to kill cancer. Many experts travel. This fundamental difference is breast-conserving treatments. However, believe that protons do a better job of what makes proton therapy preferential all of these benefits must be proven breaking the DNA than photons, and this for certain tumors. If vital organs definitively through clinical trials, is an area Laiho is eager to explore. or structures are along the path the DeWeese says, adding that these studies radiation travels, protons cause less may show cancers that can be treated “Protons damage DNA directly, and that damage to them. just as effectively with less expensive type of damage is harder for cells to therapies, but they will also reveal when repair,” says Laiho, whose research It can reduce excess radiation to normal proton is the preferable choice. focuses on understanding the benefit of cells and to vital structures and organs by about 1.5 to three times, Viswanathan Prostate cancer radiation therapy with drugs that further WEB EXCLUSIVE cripple cells’ ability to repair DNA dam- says. But at two times the cost of photon is a cancer where Listen to On Target with radiation, clinical data to prove proton’s many questions Dr. Akila Viswanathan, age. “If we combine proton therapy with Interim Director of Radiation drugs that inhibit DNA repair pathways, benefit over photon radiation is essential remain. Proton Oncology and Molecular to moving the technology forward. therapy has been Radiation Sciences: the interaction will likely be greater than http://bit.ly/2TD58vr what we see with photons.” used frequently Curtiland Deville Jr., M.D., Associate Director of the Johns Hopkins National Proton Center.

“I was drawn to the Kimmel Cancer Center because of its clinical and research expertise and patient-centered approach,” says Deville. “The goal is always to leverage this wealth of experience, bring this expertise to the community, and improve the treatment of patients.” CARE THE SIDNEY KIMMEL COMPREHENSIVE CANCER CENTER at JOHNS HOPKINS 9 Urologic Cancers and Sarcoma to treat the cancer. National trials are on- reason DeWeese and Viswanathan set Curtiland Deville specializes in the going, but currently, all available evidence up the proton center to have an unparal- treatment of urologic cancers, such as shows that both types of radiation therapy leled emphasis on research. prostate cancer, and soft tissue have equal benefit. sarcoma, a rare cancer of the soft tissues of the body. “The fundamental issue with proton for The fundamental benefit of proton prostate is do we have a clinically mean- therapy is that it has no exit dose, Deville ingful benefit that justifies its increased says, and this reduces unnecessary ra- cost?” asks Deville. Generally, he says, pho- diation exposure to surrounding normal, ton and proton therapy provide compara- healthy tissues. Proton therapy also pro- vides the potential to treat in challenging ble results for prostate cancer, but photon therapy is a less expensive treatment. clinical scenarios. When soft tissue sar- RBE helps researchers comas in the arms or legs recur, the pa- learn what doses of each type of radiation therapy tient may be spared an amputation by “I am a prostate expert,” says DeWeese. are required to produce undergoing a repeat course of radiation “I’m not sure it’s a substantial advantage the same clinical effect. One important area allowing for limb-sparing surgery. for this cancer. But that’s OK. These of research focus Deville also published the first clin- kinds of studies have to be done to deter- will be relative biological effectiveness, ical studies on the use of proton ther- mine when other forms of radiation ther- or RBE, how much more effective is pro- apy for prostate cancer after surgery. apy will work just as well at a lower cost.” ton therapy compared to photon radia- “This is an exciting area, particularly for young men who have undergone sur- tion therapy. They want to know what gery for their prostate cancer and Deville would like to study proton ther- doses of each type of radiation therapy experience recurrence in the prostate apy in younger men diagnosed with are required to produce the same clinical bed where the prostate was located,” prostate cancer, particularly those who effect. Just as important, they need to says Deville. When treating the have a recurrence after surgery. who do confirm that the prescribed dose is actu- prostate, the development of an in- not want to have surgery. Young patients ally being delivered and going where they jectable, absorbable “hydrogel” are at greatest risk of developing radia- expect it to go. spacer, protects adjacent bowel and tion-induced secondary cancers later in rectum during treatment. life, and proton therapy could prevent Linear energy transfer, or LET, is the Seminoma is a rare but highly cur- able form of testicular cancer that typ- these toxicities. Other functional charac- density at which the energy is deposited ically affects younger men. Radiation teristics could also indicate prostate can- along the path to the tumor and in may be used after surgery to reduce cer patients who may develop fewer the tumor. Protons travel the risk of or treat recurrence. Proton quality of life-impacting side effects with more quickly en route therapy may reduce the risk of second proton therapy. Patients who have re- to the tumor, depositing cancers benefiting these often young ceived radiation and could benefit from little energy or lower patients, says Deville. additional treatment, or re-radiation, is LET. The protons slow “I was drawn to the Kimmel Cancer another circumstance where the preci- inside the tumor, and Center because of its clinical and research sion of proton offers an advantage in var- that is where the highest expertise and patient-centered ap- proach,” says Deville. “The goal is always ious types of cancer. There may be density of cancer cell- to leverage this wealth of experience, patients who, in the past, would have killing energy is trans- Linear energy transfer, or LET, is the density of bring this expertise to the community, and been excluded from radiation therapy ferred or deposited, energy deposited along the path to the tumor improve the treatment of patients.” that could be beneficial against their can- explains physicist Todd and in the tumor. He likes being based at Sibley, cers because of toxicities, says Deville. McNutt, who is part of Protons travel more quickly en route to the which brings the expertise and re- the expert team that tumor, depositing little energy or lower LET. sources of a major academic univer- On the other hand, photon, with its makes the complex cal- sity to a community environment. He more scattered energy, may be the bet- culations that maximize damage to is excited about partnering with other doctors in the community and other ter choice for tumors that are not so cancer and minimize risk to healthy local institutions, such as the United precisely located but rather dispersed organs and tissue. The region where Medical Center, Howard University throughout an area of the body or the energy is the highest is right at the and Children’s National. “These clinical organ. These types of comparative stud- edge of the tumor, he says. This is why collaborations enhance our impact on ies will be standard practice at the expertise is so critical. “If you don’t get patients in the broader national capital Johns Hopkins National Proton Center. it right, the highest LET may hit outside region and beyond, providing conven- the tumor, and if there is a narrow ient access to unique care and world The lack of comparative studies between boundary between the tumor and a class treatments, such as the most ad- photon and proton therapy was a primary critical organ or structure, the patient vanced radiation therapies and clinical innovations.” may be harmed.” CONTINUED ON PAGE 12. 10 PROMISE & PROGRESS The Johns Hopkins National Proton Center What Sets Us Apart

Unparalleled Expertise: Since opening as planning and delivery of proton therapy. medicine approach that brings together all one of the first comprehensive cancer Respiratory gating technology tracks the specialists and experts to work with patients centers in the nation, the Johns Hopkins proton beam to movement of the tumor. to develop individualized, detailed treatment Kimmel Cancer Center and its experts have Our experts helped invent and develop plans specifically suited to each patient. led cancer research, deciphering the causes these technologies. of cancer and advancing care for the most Local, National and International: The complex cancer cases. This level of expertise Pencil Beam and Other Advanced Tech- location of our proton center at Sibley continues with our proton therapy center, nologies: It is one of just a few incorporating Memorial Hospital in Washington, D.C., which will be directed by the leading radiation the latest pencil beam delivery that virtually allows us to continue to bring the most oncology and medical physics experts in the paints tumors with cancer cell-killing radia- advanced cancer care to patients living in the world. tion while sparing surrounding normal tissue. region, while also providing care to patients across the U.S. and around the world. Largest and Most Advanced: Our 80,000- Research Center: It is the only academic square-foot facility is one of the largest and proton therapy center in the region and one Access for All: Collaboration among the most advanced facilities in the world, with of just a few in the world where much- Johns Hopkins Kimmel Cancer Center, four treatment gantries and dedicated needed research studies will be performed to Children’s National Hospital and Howard research and pediatric-specific space. decipher basic biological mechanisms and University ensures advanced cancer care help set the standard of care for proton to patients of all ages, including children Imaging Couch and Respiratory Gating: therapy now and for the future. and young adults, and the most It is the only proton center with CT imaging underserved communities in the region. integrated with treatment to ensure Precision Medicine: Our experts take a the most accurate and precise treatment unique multidisciplinary and precision THE SIDNEY KIMMEL COMPREHENSIVE CANCER CENTER at JOHNS HOPKINS 11

LEADING THE WAY therapy as part of their treatment.” ing dose to the surrounding normal tissues.” Meet National Proton Tsien and colleagues are excited by the Among the strategies Tsien wants to re- Center Medical Director possibilities of using proton technology to im- search is the use of ultrafast flash radiation Christina Tsien prove radiation treatment of tumors next to therapy with proton therapy to maintain high critical organs. Tsien notes that the National doses of radiation to tumors while reducing Proton Center has state-of-the-art pencil the dose to normal tissues. “This would ulti- beam technology with image guidance, which mately enable us to substantially shorten the affords physicians the ability to deliver highly length of treatment from several weeks to precise and conformal proton therapy. several days,” she says. “Johns Hopkins physicians are world- Radiation oncologists now have many dif- renowned experts in the treatment of cancer, ferent cancer-fighting tools at their disposal, and they are committed to clinical trials and and Tsien stresses the importance of select- translational research to improve the quality ing the right treatment plan for each patient. of life and outcomes for cancer patients, pro- “Proton therapy will not be suitable for viding evidence on how proton therapy can everyone, and we are committed to ensuring reduce long-term radiation side effects,” says patients receive the best and most suitable Tsien. This includes protecting the heart for treatment,” says Tsien. breast cancer patients and reducing short- “One of the most rewarding things for me and long-term effects on normal swallowing, is the opportunity to work as a treatment dry mouth, taste changes and weight loss in team, to give every patient a second look to Johns Hopkins National Proton Center Med- head and neck patients, she says. make sure nothing has been missed and that ical Director Christina Tsien, a leading brain “Treatment of brain tumors will also be a we’ve explored every possible avenue and and central nervous system tumor expert, key area of cancer care progress because of every treatment option,” she says. “We need brings a wealth of expertise to her new role. the potential to preserve vision, hearing, to identify patients who will benefit the most Tsien comes to Johns Hopkins from memory, and vital brain stem, pituitary and from proton therapy and learn more about its Washington University School of Medicine neuro-cognitive function,” says Tsien. impact on tumors and normal tissues. We in St. Louis, Missouri, where she was chief of Tsien adds that proton therapy is an excit- also need to go into the laboratory to reveal the Central Nervous System Service, director ing opportunity for patients who otherwise the cellular mechanisms that can answer of clinical research for radiation oncology, might be excluded from radiation therapy questions like why a specific treatment may and co-medical director of stereotactic radio- because of prior radiation treatments. work in one patient but not in another.” surgery and the gamma knife center. “Proton therapy is an incredibly complex Tsien says Johns Hopkins National Proton Her mission for the Johns Hopkins Na- and precise tool, and there is still much to be Center experts will work closely with col- tional Proton Center is to ensure patients re- done for experts to harness its full potential,” leagues throughout the Johns Hopkins sys- ceive outstanding individualized care, she says. “We are working to develop ad- tem as well as with colleagues at other provide the very best training opportunities vanced imaging techniques to monitor treat- organizations such as the National Institutes for faculty and staff members, and maintain ment changes in real time, allowing us to of Health. “We are aiming to provide the very an active clinical and translational research adapt radiation treatment plans. We are best patient care and to be on the forefront of program. building better motion management tools, innovative proton research,” she says. “We are bringing world-class cancer care and we want to improve our understanding As Tsien looks ahead, she also thinks back and cutting-edge research to patients here of radiation tumor biology to further increase to her own diagnosis as a young medical stu- and around the world,” says Tsien. the effectiveness of proton therapy in combi- dent with a rare type of sarcoma. It led her to The Johns Hopkins National Proton Cen- nation with systemic therapies.” pursue a career in radiation oncology. Proton ter is committed to providing pediatric and Tsien is eager to study proton therapy in therapy was not available at that time, and adult patient-centered clinical and research combination with immunotherapy, targeted her experience reminds her of the continuing programs, she says. “In collaboration with drug therapies and systemic therapy — treat- need to advance cancer therapies. She under- Children’s National, we will have a strong ments that work to zero in on specific molec- stands cancer on a professional and personal focus on improving outcomes for pediatric ular alterations that drive cancer growth and level and chose to come to the Johns Hopkins patients and reducing short-term and long- spread. National Proton Center, she says, because of term treatment side effects,” says Tsien. This “Combining proton therapy with other the opportunities uniquely set up to pursue includes using proton therapy to reduce cancer treatments may help prevent cancer novel clinical and laboratory studies using treatment-related impact on growth and cog- recurrence, and this will be an active area of state-of-the-art proton therapy with the aim nition, and the risk of secondary cancers later preclinical and clinical translational research of transforming patient care. in life, she says. in the Johns Hopkins National Proton Cen- “I am excited to be here,” says Tsien, “and “For adults, the potential impact of proton ter,” Tsien says. “Our purpose is to figure out what I’m most excited about is helping pa- therapy can also be substantial,” Tsien says. how to improve cancer survival, and often tients everywhere get the best care, and that “Radiation therapy is an integral component the best way to do that is to use different can- means we are always looking to the future of cancer care, with over half of all patients cer therapies in combination to deliver high and always moving forward. Our goal is to diagnosed with cancer receiving radiation radiation doses to the tumor while minimiz- eliminate cancer.” 12 PROMISE & PROGRESS

CONTINUED FROM PAGE 9. Better from the Start Cancer Center and make the proton therapy Even before the research begins, we provide the safest and most advanced Deville is among Kimmel Cancer Center DeWeese and Viswanathan are confident available. experts who are eager to collaborate with that the Johns Hopkins National Proton McNutt and use his Oncospace data min- Center is poised to deliver unprece- How we deliver radiation therapy at the ing system to track and compare toxicities dented care. Our 80,000-square-foot pro- Kimmel Cancer Center is already a step with photon and proton therapy to de- ton center is one of the largest in the above most other places, DeWeese says. velop a precision medicine approach. He country and has four gantries—the large, Advanced expertise has kept radiation says it could help identify prostate cancer sphere-shaped structures that house delivery very focused, conforming to the patients who would benefit from proton the equipment used to deliver proton tumors, and allowed our doctors and therapy. therapy to patients. The gantry scientists to make every type of radiation rotates around the patient, delivering the therapy technology work the best for “This is the right direction for an aca- proton beam at any angle necessary to patients while minimizing harm. demic proton center like ours. High- target the cancer. Unique features, level evidence has been lacking. Kimmel including the pencil beam, a tumor tracking To that point, DeWeese recalls a patient Cancer Center experts can bring their system that allows the beam to adjust to he treated as a resident who poignantly expertise into the research realm, and 10 tumor movement, in-room imaging via a illustrates the tradition for patient- years from now, we’ll have these answers CT Couch and the Oncospace data min- centered care and ingenuity that remain to set the standards of care,” says Deville. ing system, are all unique to the Kimmel the heartbeat of the department.

CARE Head and Neck Cancers Ana Kiess often treats cancers that occur amid confined spaces in the proximity of the brain, eyes and other vital anatomy. She plans to explore proton therapy for the treatment of salivary gland and skull-based tumors to spare the brain stem, brain and optic structures from radiation. The precision of proton therapy and the ability to stop the beam at the tumor will provide new opportunities to cure patients with advanced cancers, she says. In sinus and nasal cancers, calculating radiation dose is difficult because of the potential density changes. “The patient may have clear sinuses as treatment begins that become filled with mucus before the end of treatment,” she says. As a result, these patients require complex treatment planning, replanning and dose calculations to account for these dynamic changes. She will be collaborating with Oncospace (see page 25.) inventor Todd McNutt and others to use data to help cre- ate sophisticated advanced planning for these patients. Kiess is excited about proton therapy clinical trials for patients with these less common cancers. “Through clinical trials, we learn from each patient, improving the understanding of tox- icities and ways to improve treatment," she says. THE SIDNEY KIMMEL COMPREHENSIVE CANCER CENTER at JOHNS HOPKINS 13

In 1990, he was working with a former “I can’t think of too many places at the type of imaging called a PET scan to see faculty member, the late Moody time that had the team to innovate this that and know exactly where radiation Wharam, to treat a young patient with type of care to save this child’s eye,” says was applied that minute. Based on what the rare occurrence of an eye cancer DeWeese, adding that this remains the we see, we may deliver the dose on that called retinoblastoma in both eyes. With- type of care that every patient who comes day in one way, and the next day, use a out extraordinary measures, the young to the Kimmel Cancer Center receives. slightly different dose or angle of treat- boy was destined to lose vision in both ment or energy,” says DeWeese. eyes, DeWeese says. The only way to This dedication to patients and the ability preserve the function of one eye was to to successfully plan and deliver such a Wong worked with proton therapy devel- deliver radiation so precisely that it would complex treatment exemplifies the differ- oper Hitachi to integrate another inven- destroy the cancer without harming the ence between radiation therapy at Johns tion, called respiratory gating, that tracks anatomy of his eye. Hopkins, including proton therapy, and motion in the lung and stops the pencil radiation therapy most everywhere else. beam if the beam and tumor lose align- COLLABORATION ment due to motion caused when Advanced expertise It is these “extra lengths” that make our patients breathe. proton center unique from the start. has kept radiation “The machine only fires when the beam delivery very focused, Our proton center also has the most up- is in the right place,” says Wong. “If the to-date pencil beam technology, which tumor moves, the machine automatically conforming to the only recently became available. The stops. The beam works when it is lined tumors, and allowed pencil beam paints tumors with cancer up and stops when it is not lined up. cell-killing energy layer by layer, staying We’re the first to have it.” our doctors and within the boundaries of cancer. The scientists to make technology is so advanced that it is able Wong says the studies needed for FDA to modulate intensity, delivering varying approval of the gating technology will be every type of radiation degrees of energy based on the specific done at our National Proton Center. therapy technology makeup of the tumor. Instead of the same energy being deposited throughout the Another technology being studied by work the best for tumor, our pencil beam adjusts to differ- Wong and physicist Kai Ding further patients while ences throughout a tumor to provide the buffers vital organs right amount of energy to every different from the energy of the minimizing harm. area of the tumor. proton beam. Some tu- mors sit right next to The treatment was so complex, including Collaboration among Kimmel Cancer critical structures, and the construction of a special device for Center molecular radiation scientists and providing a buffer be-

the patient’s eye, that DeWeese recalls the manufacturer of our proton therapy DING tween the organ and coming in every morning for weeks at 6 system means our National Proton the tumor could make it safe to deliver a.m. to set up for the patient’s treatment. Center will usher more advanced tumor higher doses of radiation to the tumor, Technologies to perform this type of monitoring that makes the already safe Wong says. precise radiation treatment, like proton and targeted pencil beam patient-specific therapy and stereotactic ablative radio- and even more tumor-specific. One Ding received funding from the National surgery, had not yet been developed, so method uses molecular monitoring to Cancer Institute to study image-guided DeWeese and Wharam fashioned their evaluate the tumor and adapt radiation injection of a spacer gel to push tumors own way to get radiation to the cancer treatment to each individual patient. away from radiation-sensitive organs. For and protect the eye. It worked, and in Molecular imaging allows doctors to example, in pancreas cancer, the spacer 2017, the patient graduated from college differentiate cancer cells from scar tissue gel could be used to push the tumor away with an engineering degree. He sent or other ambiguous lesions and better from a section of the small intestine Wharam and DeWeese a family photo define the anatomy of the tumor and its called the duodenum. Protecting nearby taken at his graduation. DeWeese won- response to radiation treatment. organs would permit higher doses of ra- ders how different that family photo diation to the tumor. Studies of the spacer might have been if they had not gone to “When protons interact with human gel have already begun in photon radia- such lengths to save the patient’s vision tissue, they produce things like oxygen in tion therapy and will begin in proton in one eye. a different molecular state. We can use a when the center opens.

CONTINUED ON PAGE 17. 14 PROMISE & PROGRESS The Path to Proton Milestones in Radiation Oncology Excellence in proton therapy emanates from excellence in all areas of radiation oncology. Our National Proton Center is built upon a strong history of breakthrough discoveries and scientific ingenuity.

1973: Johns Hopkins is among the first to 1986: Our radiation oncology experts 2004: The Intensity Modulated Radiation be designated a Comprehensive Cancer become the first in the region to perform Therapy Program began to deliver high- Center by the National Cancer Institute. stereotactic brain surgery, a computer- precision radiation that conforms to the Medical oncologists, radiation oncologists, generated surgery performed without three-dimensional shapes of tumors and surgeons, oncology nurses, researchers knives, in order to destroy deep-seated delivers higher and well-defined doses and other specialists work together to tumors and blood vessel malformations of radiation to tumors, and even specific advance cancer treatment and research. in the brain. areas within tumors, while minimizing radiation to surrounding normal tissue. Radiation oncology broke off from the 1989: A new treatment delivers radioactive Department of Radiology and Radiological “seeds” into the airways, extending life for 2005: Miniature versions of the equipment Sciences and joined forces with the inoperable lung cancer patients. The same used to treat patients are created to perform Department of Oncology to make progress type of therapy, now known as brachyther- never-before-done animal research models. against a growing cancer epidemic. apy, is used to treat prostate and gyneco- These models allow researchers to study the best ways to target radiation-based 1976: A specialty cancer program for pedi- logic cancers. treatments to tumors and, at the same time, atric patients is established. The National 1993: Investigators discover that prevent damage to normal cells. Cancer Institute appoints Kimmel Cancer chemotherapy and radiation therapy Center radiation oncologist to two national administered prior to surgery improve 2006: Research reveals that lower doses study groups investigating childhood cancer. success rates in some cancer patients. of radiation may kill more cancer cells by eluding a protein called ATM, a damage 1977: Johns Hopkins’ program was 1994: The Kimmel Cancer Center becomes detection mechanism for cancer cells. viewed as one of the few strong academic one of the first in the nation to use a 3D programs in radiation oncology in the U.S. radiation simulation for more precisely Science Watch newsletter dubs the Kimmel This expertise attracted so many patients, planned radiation therapy. Cancer Center a “cancer research power- house,” as its research is the most often the radiation oncology clinic had to expand 2001: A combined chemotherapy/radiation cited in all of cancer research worldwide. to twice its original size to accommodate regimen preserves the voice box for many the growing patient load. laryngeal cancer patients with success rates 2007: The stereotactic body radiation ther- 1980: A Kimmel Cancer Center radiation equal to surgical removal of the voice box apy program starts. This knifeless surgery oncologist is named director of the and significant improvement in quality of life. uses highly focused beams of radiation to ablate tumors. radiation oncology committee of the 2003: The Department of Radiation Pediatric Oncology Group, a position he Oncology and Molecular Radiation 2008: Molecular Radiation Sciences research held for 10 years. He was among the first Sciences is established. accelerated to decipher the biology of DNA to study toxicities and late effects of damage response to radiation therapy and radiation therapy on pediatric patients. how cells sense and repair this damage. Research showed that men whose tumors recurred after prostate cancer surgery are three times more likely to survive their disease long term if they underwent radiation therapy within two years of the recurrence. THE SIDNEY KIMMEL COMPREHENSIVE CANCER CENTER at JOHNS HOPKINS 15

2009: A computer-assisted version of 2013: The Johns Hopkins application to 2015: The Kimmel Cancer Center at Sibley brachytherapy, a prostate cancer therapy build the largest and one of the most partners with United Medical Center and that uses radioactive seeds inserted in the advanced proton therapy centers in the Howard University to bring cancer care to prostate to kill cancer cells, is developed. country is approved. the most underserved Washington, D.C., The innovation allows for more precise 2014: An interdisciplinary research neighborhoods. placement of seeds. An even more precise collaboration reveals that testosterone, 2016: The Kimmel Cancer Center at Sibley version followed, using an MRI-assisted ro- a hormone prostate cancer cells need to Memorial Hospital opens adding medical botic needle to accurately insert the seeds. survive, can also form breaks in the DNA oncology and surgical oncology to the 2010: A technique to keep normal and that would make cancer cells more vulner- already established and growing radiation cancerous tissue surgically removed from able to treatment with radiation therapy. oncology program. The 36,000-square-foot the prostate alive and functioning for up to 2015: A unique collaboration between facility brings patients the most advanced a week is developed to allow investigators our Department of Radiation Oncology at radiation therapy technologies, latest to test anticancer therapies on live tissue. Sibley and Children’s National pediatric techniques and innovative treatments— 2010: Sibley Memorial Hospital in cancer center results in the first dedicated the same techniques and technologies used Washington, D.C., becomes part of the pediatric radiation oncology program in the throughout the Johns Hopkins Johns Hopkins Health System. national capital region. It brings together Kimmel Cancer Center. 2011: Our experts led the first-ever, in-depth, pediatric medical and surgical oncology 2017: A pioneering new therapy uses scientifically based safety analysis of experts from Children’s National and pedi- CT- and MRI-guided brachytherapy to radiation oncology and reported that a atric radiation oncology experts from the treat cervical cancer and other gynecologic combination of approximately six common Kimmel Cancer Center to provide compre- cancers. quality assurance measures could have hensive pediatric cancer care, including 2018: U.S. News & World Report prevented more than 90 percent of the po- clinical trials, to patients in the region. continues to rank the Kimmel Cancer tential incidents. Stereotactic radiotherapy is shown to Center as one of the top cancer hospitals 2012: A new, never-described compound augment immune response in pancreatic in the nation and the top-ranked center known as BMH-21 destroyed critical cancer patients. in the mid-Atlantic region. Our pediatric communication between cancer cells and oncology program is also ranked among the POLI pathway, necessary for cancer the top five in the nation. cell survival. 2019: The Johns Hopkins National Proton Center opens, bringing the most advanced proton technology, expertise and research to the region. On the Web What is Proton Therapy? Watch our informative introduction to proton therapy – the precision radiation therapy: http://bit.ly/2TD58vr 16 PROMISE & PROGRESS

COLLABORATION A New Approach for Advanced Cancers Patients like David with advanced cancers are benefiting from a new, first-of-its-kind Cancer Invasion and Metastasis Program, co-directed by radiation oncologist Phuoc Tran. The new research tackles cancer spread head on—the cause of more than 90% of cancer deaths.

Tran believes cutting off the metastatic or spreading cancer cells from the primary tumor makes it more difficult for a cancer to survive. Tran and colleagues are shifting the treat- ment paradigm for advanced cancers, using treatments, like surgery, from which patients with advanced cancers have historically been excluded, and combining chemotherapy, targeted drug therapies, surgery and radiation therapy, including proton therapy, to transform the management of advanced cancers. THE SIDNEY KIMMEL COMPREHENSIVE CANCER CENTER at JOHNS HOPKINS 17

CONTINUED FROM PAGE 13.

The Inventor ton therapy, or any radiation therapy, for proton therapy over the more scattered Affable and brilliant, Wong’s energy and that matter. It is the expertise, experience photon beam. However, the beam— his excitement for the and in-depth knowledge that allow him no matter how precise—is only as good as field are infectious. He to optimize a new technology to work its guidance system. Simply put, it will hit moves between meet- better for the radiation oncologists, what it’s directed to hit, which is why for ings with young up-and- physicists, nurses and technicians who most of his career, Wong has focused on coming physicists in his use it and—his main goal—to advance the the development of better imaging tech- office to the stairwell as care of patients. nologies that show where the beam is he scurries to the treat- going. WONG ment areas to see his in- Most places acquire proton therapy by ventions in practice and interacts with contracting someone else to build it for INNOVATION clinicians who can describe existing short- them. Wong and his Kimmel Cancer “Conventional photon falls. Along the path, he stops to talk to fac- Center colleagues took a different ulty members, nurses, technicians, approach, partnering with manufacturer radiation therapy and residents and fellows. He is always think- Hitachi to design and build a one-of- proton therapy cure ing about how he can make radiation ther- a-kind proton therapy system that apy better. More impressively, he has exceeds every other proton center in its tumors at the same rate. turned these ideas into revolutionary ad- scope, size and capability. The side effects they vances in the field of radiation oncology and molecular radiation sciences. “We have always been innovators in the can cause are similar, Kimmel Cancer Center. There are few but with proton, less John Wong’s Inventions places like us, but this is how leading 1997: Active Breathing Coordinator, an institutions like Johns Hopkins should be dose goes to normal interactive and noninvasive device, coordi- driving the development of technology. nates breathing with radiation treatment, cells. That’s the benefit.” When we see a clinical problem, we solve locking a breath in place for a short, comfortable period to prevent movement- it ourselves,” says Wong. “I look for log- related radiation damage to vital organs, ical ways to make equipment work better, The National Proton Center has mag- such as the heart or lungs. which allows researchers to dig deeper netic resonance, or MR, and CT imaging, 2000: Co-inventor of cone beam computed and move faster so they can get improved as well as a new type of CT scan called tomography, which uses a cone of divergent treatments to patients.” dual energy CT that provides detailed X-rays and captures CT images to deliver information on the specific makeup of a clear images of bone, soft tissue and tumor Most of Wong’s inventions over more tumor. This advanced and unmatched to guide radiation delivery. than three decades are centered on imag- imaging makes our proton therapy the 2001: The Small Animal Radiation Re- ing that makes sure the potent radiation most precise of any available today. search Platform (SARRP) is a miniaturized beam hits its intended cancer target. version of the human machine and made it His latest invention, the CT Couch, possible, for the first time, to study human therapies in animal models. The protection of normal tissue and brings new technology to photon and organs is at the center of most everything proton therapy by putting the image 2013: The Raven quality assurance device our experts do in treating patients with guidance directly on the therapy ma- connects to machines and quickly performs a series of measurements to ensure radiation therapy. There is no question chines. Typically in radiation therapy, pa- machines are functioning correctly. that radiation kills cancer cells. tients must move between a simulator Researchers have understood that since and the treatment room. The simulator is 2018: CT Couch integrates image guidance with treatment delivery. 1896. At issue is how it can be used to kill a dress rehearsal of sorts that uses CT im- cancer without harming normal cells to aging so that the physicists and the treat- “It’s great to be paid to sit and think,” he prevent toxic side effects at the time of ment team can visualize where tumors jokes. treatment, particularly for pediatric and are located in relation to the rest of the young adult patients, down the road, body, particularly vital organs. Complex He rarely believes a new technology is when excess doses of radiation can result calculations are made based on these adequate “out of the box,” and proton in long-term side effects or cause second imaging data, and the treatment plan is therapy was no exception. His inventions cancers to develop. set in place. Until now, treatment plan- make existing technologies better, safer ning and treatment delivery could not be and more precise. He epitomizes the The ability to direct the beam to a tumor, done in the same room and usually not on intangible component so essential to pro- and only the tumor, is the advantage of the same day. CONTINUED ON PAGE 24. 18 PROMISE & PROGRESS

Lawrence Kleinberg, M.D., (right) and patient Jeanie.

CARE Kimmel Cancer Center. There, she under- went a hysterectomy to treat the endome- Beating Brain Tumors trial cancer. Radiation oncologist and brain tumor expert Lawrence Kleinberg and neurosurgeon Chetan Bettegowda treated the spreading cancer in her brain. When friends asked Jeanie if she planned to get a second opinion, she responded, “After you’ve gotten your first opinion at Johns Hopkins, you don’t need a second opinion,” noting that she had a team of more than a dozen experts collaborating on her care.

Kleinberg offered optimism when most Jeanie (right) and partner Jenny saw her advancing cancer as hopeless. “My friends thought I was a goner, but When Jeanie, a housepainter, began having Dr. Kleinberg always believed I had a trouble pouring paints without spilling chance, and that meant so much to me,” them, the active 65-year-old chalked the says Jeanie. coordination problem up to age. Still, she couldn’t understand why she had no prob- Despite what seemed a bleak diagnosis, lem riding the waves on her boogie board four years later Jeanie's cancer is now un- but struggled to paint in a straight line or detectable. “I’m a bit of a miracle,” says back her car out of a driveway. Worried Jeanie, who just celebrated her 69th birth- Jeanie may have had a stroke, her sister day. After the combination of chemother- encouraged her to see a doctor, and the apy, radiation therapy and surgery used to news was shocking. The cause of her symp- treat the advanced cancer, she went toms was three tumors in her brain that had through physical therapy for balance and spread there from an advanced endometrial coordination issues caused by the brain tu- cancer Jeanie never knew she had. mors but says, “My treatment at Johns Hopkins was a breeze.” Jeanie knew her diagnosis was unusual and dire, so the Kent Narrows, Maryland, Today, Jeanie is back to work and playing resident opted to go to the Johns Hopkins drums with her band the Surf Jaguars. THE SIDNEY KIMMEL COMPREHENSIVE CANCER CENTER at JOHNS HOPKINS 19

Brain Tumors cells surrounding the tumor from injury,” “We have expertise in all of these Kleinberg explains. options, and this is important because Radiation oncologist Lawrence Kleinberg Comparing proton treatment to pho- proton may be better in some situations, and understands the gravity of the cancer he ton therapies will be one area of research in in other instances, we may want to give big specializes in treating. The brain tumor expert the Johns Hopkins National Proton Center. bursts of radiation over a shorter period of knows there is not only vital functional The studies will be very different for time, and in that case, other types of treat- consequences of treatment, including loss of the adult patients Kleinberg treats than ment may protect the brain better. It’s very vision or use of arms or legs, but there pediatric patients. “We know for certain that individualized,” says Kleinberg. is also a certain sanctity when it comes to there are toxicities for pediatric patients Like proton therapy, some of our the brain. It is what makes us truly human, whose brains are still developing, but we other radiation treatment devices also have the keeper of our personality, thoughts and don’t know yet the extent of these toxicities tumor tracking to make sure the radiation memories. The world’s greatest supercom- in adult patients whose brains are already beam stays fixed to the tumor, even if the puter makes the connections for essentially formed. We will only learn this by doing patient moves. This is even more vital for every bodily process and function. When research studies that compare proton brain tumors, Kleinberg explains, where tox- cancer and benign tumors infiltrate the brain, therapy to other types of radiation treat- icities to normal brain can have life- the consequences of treatment can often be ment,” says Kleinberg. altering consequences. Comparing the as dire as the diagnosis. tumor tracking in proton verses other types “The type of damage that can be of radiation treatment, such as Cyberknife, caused by radiation therapy depends on As protons travel through the body, most of the energy is another focus of research in the proton is reserved and released where the protons stop in the tumor. where in brain the tumor is located,” says Photons, on the other hand, release energy along the entire therapy center. Kleinberg. “It could affect almost any function path they travel. This fundamental difference is what makes The ability of the proton beam to stop proton therapy preferential for certain tumors in the spinal cord —strength of an arm or leg, memory function, and the brain. If vital organs or structures are along the path at the tumor makes it the preferable or even vision. Almost anything the brain the radiation travels, protons cause less damage to them. option for patients with tumors that sit on And there is no exit dose. controls could be affected.” or close to the spine or near other critical As a result, Kleinberg is excited about Photon structures that need to be shielded from the opportunities to explore the great promise therapy radiation, such as the optic nerve. Kleinberg of proton therapy for protecting the brain says proton therapy may also be the from these side effects. best option to preserve fertility in women of The patients most likely to benefit, he childbearing age who have tumors near the says, are those with brain tumors classified pituitary gland. Whether proton therapy is ENTRANCE as low grade because they are slow growing, DOSE the best option will be an individualized de- limited to a specific area of the brain, highly cision, depending upon the shape and type treatable and often curable. These charac- of tumor. teristics make them good candidates for TUMOR TARGET Its toxicity-limiting precision also pro- treatment with radiation, including proton vides flexibility to increase doses. With other therapy. These characteristics also distin- types of radiation treatment, doctors may de- guish low-grade tumors from their highly LESS MORE crease the radiation dose to the tumor to pro- malignant and aggressive counterpart that RADIATION LEVELS tect a vital structure nearby. “Proton therapy reach throughout the brain. Whether the pre- in some situations will allow us to give a better cision of the proton beam will benefit pa- Proton therapeutic dose without worrying about tients with these types of brain tumors is therapy damage to nearby structures, and that could more uncertain and will require extensive re- improve outcome for some patients,” he says. search studies. Kleinberg would also like to study ENTRANCE “The problem with highly malignant DOSE proton therapy’s ability to instigate the tumors is that what we are treating on body’s own natural defenses—the immune purpose is mixed in with the normal brain,” system—to attack brain tumors. TUMOR TARGET says Kleinberg. Having another tool to consider in treat-

Low-grade tumors, such as menin- BRAIN IS NOT ing his patients is a good thing, but he says pa- EXPOSED TO gioma (a benign tumor that forms on mem- RADIATION tients come to the Kimmel Cancer Center branes that cover the brain and spinal cord because of its reputation for excellence. just inside the skull) and pilocytic astrocy- “Our patients aren’t just looking for the toma (a slow-growing type of glioma brain next new technology. They are much more tumor that originates from star-shaped cells For example, Kleinberg says, engaged with our expertise and knowledge, called astrocytes) are more confined to a stereotactive ablative radiation or robotic ra- as are the physicians who refer them to us. specific area of the brain. diation treatment with the Cyberknife, also That is key,” says Kleinberg. “Patients often “Proton therapy will probably not be protect normal tissue. Research will show come a long way and pass a lot of centers any better at controlling the tumor, but it may the situations where proton therapy will pro- to get to us. They do this because we have do better job of protecting normal brain vide greater protection. earned that trust.” 20 PROMISE & PROGRESS

known as a metastatic cancer that often Curing Cancers Once limits the kind of treatments a patient is eligible to receive. It also often represents Thought Incurable a dividing line between a curable cancer and one that is not curable. However, Tran is beginning to shift that paradigm through a new Cancer Metastasis and Invasion Program he leads with Kimmel Cancer Center colleagues, cell biologist Andrew Ewald and Bloomberg Distin- guished Professor Ashani Weeraratna.

Their research shows that just as there are varying stages and grades of cancer, there are also varying degrees of metasta- sis. A cancer that has just begun to spread from the primary tumor to a few sites is very different from a cancer that has spread to many distant sites throughout the body, yet treatment is often similar, Tran explains. Popular opinion was that once a cancer had spread, there was no going back. Attempts to cure the cancer were obviated for palliative treatments that knocked the cancer back a bit and ameliorated pain and other side effects associated with the spread of the cancer.

Tran and colleagues, including prostate cancer researcher Kenneth Pienta, how-

“How proton therapy interacts with ever, were starting to see evidence that other therapies we already give, there was connectivity between primary including immunotherapy, represents a whole untapped area of research. tumors and cancer cells that broke away Combining proton therapy with other treatments is a completely and formed new tumors elsewhere in the novel and promising strategy to change proton therapy into a body. They believed that selectively treat- systemic treatment against more ing these tumors with radiation and other advanced, spreading cancers.” —Phuoc Tran, M.D., Ph.D. treatments had the potential to make cancers once thought incurable, curable. Brian’s days were busy as he and his wife “He said Johns Hopkins was excellent. This was the approach taken with Brian. enjoyed their active 2-year-old son. He sort of joked with me at first saying, ‘I Despite a family history of prostate won’t be offended if you don’t go, but I Tran uses the analogy of the first Ameri- cancer, when the 47-year-old began feel- highly recommend it. Scratch that, he can colonists. Although, they set up com- ing “a little off,” he didn’t initially think said, I will be offended if you don’t go,’” munities in distant locations, they often much of it. As his symptoms worsened, recalls Brian. He took the advice, and to relied upon and received support, however, Brian decided to make an this day, he remains grateful to his friend guidance and instruction from Great appointment with a urologist. for the recommendation. Britain, says Tran. Similarly, he believes— and research is beginning to bear this The urologist performed a prostate exam His appointment with the Prostate Cancer out—that spreading cancers remain and a prostate-specific antigen (PSA), a Multidisciplinary Clinic involved all of molecularly connected to the primary blood test that screens for prostate can- the specialists involved in treating tumor site, where the cancer originated. cer. The results of both tests pointed to prostate cancer, including radiation on- cancer. The exam revealed an enlarged cologist Phuoc Tran. “Most experts forget about the primary prostate, and his PSA test results were prostate tumor once a cancer has spread,” high. A friend recommended he go to By the time Brian’s cancer was diagnosed says Tran. “We’ve learned from data Johns Hopkins to have it checked out. in 2016, it had already spread, a distinction generated by the Johns Hopkins Rapid THE SIDNEY KIMMEL COMPREHENSIVE CANCER CENTER at JOHNS HOPKINS 21

Autopsy Program that some metastatic Typically, surgery is not an option for treatment against more advanced, cells go back to the prostate and travel all prostate cancer that has already spread. spreading cancers.” over, communicating with other cancer Instead, doctors usually opt to cut off the cells and colonizing. Information is testosterone feeding the cancer, a treat- It is called the abscopal effect, Tran ex- exchanged, and it strengthens the cancer ment that can quiet the cancer down but plains. The thought behind it is that as a whole,” he says. also have unfavorable side effects for treating the primary tumor and some patients, and it does not cure the cancer. metastatic lesions can cause even This connectivity and how the primary untreated tumors to shrink. It goes back tumor communicates with colonizing Tran believes cutting to Tran’s concept that the primary and metastatic tumors are not yet fully under- spreading cancer cells are interconnected, stood. Although cancer metastasis is the off the metastatic or and damaging one link in this chain is leading cause of cancer death—account- spreading cancer cells enough to weaken the entire cancer. ing for 90%—little research is aimed at figuring out how to thwart it. Deciphering from the primary tumor “The sum is greater than the individual how cancer spreads and how to interfere makes it more difficult parts,” says Tran. “Cut off the metastatic with the process is the mission of the sites from the primary tumor, and it Cancer Invasion and Metastasis Program. for a cancer to survive. becomes more difficult for the cancer Some prostate clinical to survive.” Cancer cells are the ultimate survivalists, exploiting all the tools of normal cellular trials are beginning to The treatment appears to be working for and molecular biology to their advantage. prove his hypothesis to Brian, who four years later remains can- There are some data that show that pri- cer-free, with no signs of recurrence and a mary tumors send out signals to lay the be tre, showing that PSA of zero. He does his part to keep the groundwork for the future spread of the treating the primary cancer in check, keeping active, eating well cancer. Later, cells go to predetermined and keeping a positive outlook. locations and form new tumors. Other tu- tumor extends life. mors remain dormant, sometimes for “One of the smartest things I did was come decades, and then begin growing again. Tran says as they shift the treatment to the Johns Hopkins Kimmel Cancer paradigm for metastatic cancers, they Center,” says Brian, who got a second opin- “Communication is cut off, and the cancer need safe and precise ways to get at ion at Tran’s encouragement. Troisi went is barely surviving, but then communica- spreading tumors, and he believes proton to another major comprehensive cancer tion is restored,” Tran hypothesizes. “The therapy could be the way. Treatments center and was advised to stick with Tran’s cancer may just be sitting there, not actively such as immunotherapies that engage and plan. The doctor he saw noted that no dividing, but then some event allows it to improve the ability of the immune system other place was offering these kinds of take off again. That’s what we need to stop.” to attack cancer are having success against treatments for advanced prostate cancer. metastatic cancers and may be part of Tran believes cutting off the metastatic or combined treatments. “We think that “The most important advice I give to spreading cancer cells from the primary protons are less immunosuppressive, so other people is to make sure to talk to the tumor makes it more difficult for a cancer we want to study how they interact with best,” says Brian. “Find the people who to survive. Some prostate clinical trials immunotherapy,” says Tran. care about the issue you have and are on are beginning to prove his hypothesis to the cutting edge. I met people around the be true, showing that treating the primary He and Marikki Laiho, director of mo- world when I was receiving radiation tumor extends life. Still, many times the lecular radiation sciences, have already therapy at the Kimmel Cancer Center. cancer often comes back, he says. begun preparing for these kinds of proton They told me that everyone around the therapy laboratory studies. world knows Johns Hopkins.” Tran’s vision is to take the battle to the next step, treating both the primary “We don’t really know a lot about pro- Tran says many patients he sees for the tumor and metastatic sites. tons. This is our mandate. How proton first time come believing there is nothing therapy interacts with other therapies we that can be done for them. In their most This is the plan Tran, Pienta and surgeon already give, including immunotherapy, difficult moment, Tran’s innovative new Mohamad Allaf developed for Brian, represents a whole untapped area of re- treatment approach gives hope. combining chemotherapy, a testosterone- search,” says Tran. “Combining proton blocking drug, surgery and radiation to therapy with other treatments is a “My life is great,” says Brian. “I have two get at the primary tumor and the spread- completely novel and promising strategy kids now, and my wife and I are enjoying ing cancer cells. to change proton therapy into a systemic every moment.” 22 PROMISE & PROGRESS

INNOVATION Better Treatment for Head and Neck Cancers

In 2018, a cancerous tumor David had “Every person I talked to prepared me for removed from his neck a decade earlier pain and suffering,” says David. “Dr. Quon returned. was different, and that sold me.”

David’s cancer was classified as HPV-pos- While most cancer experts David itive, meaning it was caused by the human consulted considered severe side effects a papillomavirus. Kimmel Cancer Center given, Quon took a different view. “We researchers identified the virus as the don’t want you to be in pain. We want you driver of certain head and neck cancers in to eat,” Quon told David. His goal was to 2007. Their findings marked a distinct minimize or eliminate side effects, and subtype of head and neck cancer and one David said that made the Kimmel Cancer that portended better responses to treat- Center’s approach unique. ment and very high cure rates. At the heart of what sets Quon’s approach Patient David from others is a desire to do better for patients, and this resulted in a program called Oncospace he developed with physicist Todd McNutt. Head and neck cancers are considered among the most difficult to treat because they are in close proximity to so many other organs and glands. Damage to the voice box, tongue, throat and salivary glands can make it painful for patients to eat and As an engineer, David looked at things cause other quality-of-life-altering and pragmatically and analytically, and he did even life-threatening consequences. his research. He consulted with his doctors in Hong Kong, where he’d lived McNutt and Quon developed a complex, since 1995 and had his first surgery. They computerized data mining system that told him HPV-positive head and neck scrutinizes and analyzes data from prior cancer was uncommon in Hong Kong. At patients who received radiation treatment their suggestion, he began considering to improve the treatment of new patients. treatment back in the U.S., where he often It evaluates the therapies that worked best traveled for business. He contacted for a particular cancer and learns from experts at the National Cancer Institute those that resulted in less-than-favorable (NCI) and at several NCI-designated outcomes to generate an optimal comprehensive cancer centers. treatment plan. Quon used Oncospace to develop a plan that protected David’s He began receiving a standard regimen of parotid gland from permanent damage. chemotherapy in Hong Kong as he explored radiation therapy options, includ- David says he is grateful to Quon and ing proton therapy. David’s oncologist told nurse Marsha Freudigman for focusing him he had accepted a position at Johns on the person and not the cancer. David Hopkins and introduced David to Kimmel continued to work and remained active Cancer Center radiation oncologist and throughout his treatment, exercising and head and neck cancer expert Harry Quon. using yoga, reiki and acupuncture to support healing. “After six weeks of David’s cancer was at the base of his radiation therapy, I was eating just like tongue and a saliva-producing gland called anyone else,” says David. Even better, the parotid. David’s last scans show no signs of cancer. THE SIDNEY KIMMEL COMPREHENSIVE CANCER CENTER at JOHNS HOPKINS 23

Harry Quon, M.D.

Oncospace scrutinizes and analyzes data from prior patients who received radiation treatment to improve the treatment of new patients. 24 PROMISE & PROGRESS

CONTINUED FROM PAGE 17. Just as the trajectory of the beam is only The proton therapy CT Couch will inte- Comparative Planning as good as the guidance system, the grate radiation simulation with radiation To use proton or not to use proton is the image guidance is only as good as the treatment, and because Wong is the question that few centers can solve. quality of the images it receives. Imaging inventor, his patented technology will be resolution has been a challenge that often unique to the Kimmel Cancer Center’s “We own all of our machines, so we are leads to a larger field of radiation treat- radiation oncology clinics, including the not driven by profit to select one machine ment to ensure that cancer cells aren’t National Proton Center. over others. Patient care—whatever is the missed. best option for the patient—will guide The idea to integrate imaging with this decision-making,” says Viswanathan. “Imaging is critical to the process. The therapy came to him when he observed better you can see the target, the more colleague Viswanathan’s novel 3D image- The Kimmel Cancer Center’s excellence precisely you can treat with radiation,” guided brachytherapy. One part involves in all areas of radiation therapy makes it says Wong. “If I don’t know where the advanced MRI guidance, and the other possible to offer comparative planning. tumor is, it doesn’t matter how great the uses mobile CT to check the placement of This means the ability to determine equipment is.” He says proton therapy the implant every day to confirm the which one of its many radiation treat- has been delivered for many years with- location of the radioactive seeds that treat ment tools—proton, photon, CT- and out absolutely knowing for sure where cervical, uterine and vaginal cancers. MRI-guided brachytherapy, stereotactic the beam is hitting. ablative radiation, Cyberknife—is the “It made me realize you could do CT im- best option for each patient. aging with a small footprint,” he says. This “We own all of small footprint makes it possible to bring “The kind of radiation our experts per- our machines, so imaging into the treatment room without form is already very focused in conforming interfering with the treatment equipment. to the tumors. Some centers have been we are not driven so proton focused they are missing the by profit to select “This is precision therapy in practice,” benefits of other types of radiation,” says says DeWeese. “Patients’ tumors are in Viswanathan. “Proton therapy, for exam- one machine over their bodies in a specific orientation, and ple, cannot substitute for stereotactic others. Patient this differs patient by patient. One size ablative radiotherapy, so the benefit of an doesn’t fit all,” he explains. “We have to expert team who can make the important care—whatever is target each patient’s cancer differently, comparisons and correctly determine, the best option and we do this based on a sophisticated patient by patient, which form of radia- set of scans before patients are treated. tion therapy is the optimal choice cannot for the patient— Those images are fused together, sort of be overstated.” will guide this like virtual reality, so we know precisely where in the body the tumor is in Stereotactic ablative radiotherapy involves decision-making.” relationship to the normal cells around it.” many weaker beams that come from a variety of directions and converge at The CT Couch addresses this problem, DeWeese says a CT scan of a patient is the tumor to deliver a more precise, introducing—for the first time—practical done to see where cancer is on the day of higher-dose beam to the cancer. in-room imaging. Some refer to it as on- treatment relative to where it was deter- board imaging, but Wong prefers CT mined to be in treatment planning. All of This kind of comparative planning is Couch because of an essential compo- the images are merged to precisely aim another unique service of the Johns Hopkins nent—the couch is part of the therapy the beam within an incredible one-tenth National Proton Center. For each patient, machine, but it is not on the therapy ma- of 1 millimeter accuracy. it involves analysis of imaging and treat- chine so it does not disturb or interfere ment plans for each machine to deter- with any of the treatment machinery. The CT Couch will be integrated into mine which type of radiation therapy is The image quality is comparable to diag- both photon and proton therapy, helping the best approach. Sometimes it may be nostic-quality CT and far superior to ensure the treatment beam goes a combination. cone beam CT—one of Wong’s earlier in- where it is intended, and perhaps more ventions—and other existing imaging importantly, avoiding critical organs and Every type of radiation therapy has its technologies. structures that need to be protected from place, but most centers lack the capability radiation treatment. to use data and science to make those judgments. “It’s not always obvious,” says THE SIDNEY KIMMEL COMPREHENSIVE CANCER CENTER at JOHNS HOPKINS 25

DeWeese, “so this is another area where expertise is vitally important. All plans are not created equally.”

“There are some cancers, such as those in the brain or near vital organs, that should get proton therapy, but there are other cancers that would respond better to photon therapy,” explains Viswanathan. “Some patients might benefit from a com- bination of both. We may want to treat the main tumor with photons and metastatic sites or lymph nodes with protons.”

Working with our radiation oncologists, our medical physicists use supercomput- ers to iterate the plans hundreds of times to arrive at the most ideal way to deliver radiation to each patient. The selected plan is reviewed, modifications are made and it is tested with a virtual avatar of the patient to be sure it has the outcomes an- ticipated. The end product is precision radiation therapy that has been detailed and confirmed at many levels and specific to the needs of each patient. Oncospace and Proton Further informing these decisions is a Kimmel Cancer Center-built data mining system called Oncospace.

This complex system scrutinizes and an- alyzes data from prior patients who re- ceived radiation treatment to improve the treatment of new patients. It evalu- ates the therapies that worked best for a particular cancer and learns from those that resulted in less-than-favorable out- comes to generate an optimal treatment plan.

Ten years in the making, Oncospace was piloted in head and neck cancers, which are among the most difficult cancers for radiation physicists and oncologists to plan for, says radiation physicist Todd McNutt, who built the technology. It often requires many revisions to design a treatment that hits the cancer with INNOVATION A technology called Oncospace, radiation but does not do damage to vital developed by physicist Todd McNutt, organs and glands, such as the voice box Ph.D., compares outcomes to determine when and in which patients and salivary glands, he says. proton therapy is the best option.

CONTINUED ON PAGE 27. 26 PROMISE & PROGRESS

CARE Kimmel in the Community

Howard Hopkins Partnership

The opening of the Johns Hopkins National Proton Center will also mark the start of a collaborative medical physics program with Howard University.

Theodore DeWeese and John Wong collaborated with Quinton Williams, chair of the physics and astronomy department, and Prabhakar Misra, professor of physics, at Howard University, a historically black university in Washington, D.C., to get the program up and running.

“Howard University has a top notch under- Unity Health Care graduate program in physics and engineering with outstanding students,” says DeWeese. A collaboration between Unity Health Care and Johns Hopkins “These are exactly the kinds of students Sibley Memorial Hospital brings a cancer clinic to underserved who will excel in our joint program and communities in Washington, D.C. The specialty services offered become great contributors to the field.” through this collaboration will provide much-needed cancer care to underserved patients in Wards 7 and 8, who have some of the Wong and other Kimmel Cancer Center highest cancer rates in the country, and other areas throughout physicists will be among the faculty of the the District of Columbia. new program. DeWeese approached Wayne Frederick, president of Howard University The Parkside Health Center will serve as home base for the clinic. with the idea when he noticed there were A nurse navigator will help patients overcome barriers to care and very few African Americans among the 4,000 facilitate timely access to treatment at the Johns Hopkins Kimmel members of the professional society for Cancer Center and Johns Hopkins National Proton Center. medical physicists. THE SIDNEY KIMMEL COMPREHENSIVE CANCER CENTER at JOHNS HOPKINS 27

CONTINUED FROM PAGE 25.

With such vulnerable anatomy close vividly colored computerized maps and the myriad of contributing factors to make to the tumor, radiation can impact the graphs; and reveals the optimal plan. At these incredibly complex calculations. function of untreated glands as much as the same time, it takes into account and the treated glands, explains McNutt. connects all of the variables—age, underly- McNutt is now beginning to apply the Instead of looking at each gland as an in- ing health conditions and other treatments same analytical tools to decrease swal- dependent organ, he says Oncospace patients are receiving—and figures out lowing problems, potentially life-threat- helps them analyze it all together. It’s how all of these variables relate and influ- ening scarring of the larynx and the less called inter-organ dependency, and he ence toxicities and response to treatment. serious but nonetheless troubling impact and collaborators, like head and neck on taste for head and neck cancer cancer expert Harry Quon, are the first to They are even exploring the physiologi- patients getting radiation. They are also use such complex computer analysis to un- cal features of glands and the potential exploring how to use Oncospace to derstand it and improve care for patients. role they play. Information like texture, predict risk of cancer recurrence, fat content, fibrous connective tissue and which patients will likely benefit “All of these glands work together to pro- around glands and overall health of sali- from treatment with immunotherapy, duce saliva. If I give a high dose of radia- vary glands are entered into Oncospace and identify patients who would most tion to one gland, we have to know how to help guide individualized treatment benefit from receiving radiation therapy much function we have to preserve in all plans for patients. after surgery. Oncospace is also being ex- of these other glands to keep salivary panded to mine other cancers, including production at a comfortable level,” says Oncospace uses a type of artificial intel- esophageal, lung, pancreatic, prostate McNutt. “If I overdose this ductal region, ligence known as machine learning to and pediatric cancers, with the goal of I may render some portion of the rest of look back at the patterns of dose within using it to inform the treatment of every the gland useless.” Although the gland the anatomy and how these doses related cancer type. Ultimately, he would like to may still function, it blocks the flow of to patient outcomes. In head and neck make the technology available to experts saliva, making it difficult to eat, causing cancer, McNutt and Quon know there are throughout the U.S. and the world. pain and often leading to oral infections. stem cells throughout the glands that ini- tiate the healing that keeps the glands Oncospace quantifies, measures and an- healthy. By querying Oncospace, they “Now when we have alyzes all of the variations in treatments found that varying the dose of radiation to give radiation close and toxicities in patients already treated may be the key to protecting these stem to inform the care of new patients. Every cells and ensuring that salivary function to areas that we think patient treated adds to the data, so it is returns after radiation. contain these repair ever improving as new data—and more types of data, such as physician notes and “This is one of the things we are most stem cells, we have the imaging—are included. excited about studying in the proton cen- capability to stop the ter,” says Quon. “Now when we have to “There is knowledge in the variations in give radiation close to areas that we think proton beam on a dime.” toxicities and response that occur from contain these repair stem cells, we have the patient to patient, and this type of analysis capability to stop the proton beam on a Experts from Japan, a country with a is only possible with the analytic capabil- dime. That makes it possible for us to keep long history of treating cancer with ities of Oncospace,” says Quon. radiation at a low dose in these critical proton therapy, are coming to the stem cell regions. It gives us some new Kimmel Cancer Center to collaborate It’s a tool that no other cancer center in options.” with McNutt and discuss including their the world has, and Quon says it has been data in the system. instrumental in improving patient care. Proton therapy, he says, offers the ability He credits it with attracting people to the to improve patterns of dose because it is “The truth is no one can keep treating Kimmel Cancer Center’s head and neck so targeted. Oncospace also compares with protons without the evidence and cancer practice. photon and proton treatment outcomes guidance Oncospace provides,” Quon to determine when and in which patients says. He hopes other proton centers will McNutt’s system provides the guidance proton is preferable and when photon want to collaborate. that allows Quon and other clinicians to may be the better option. It is one more maximize healing and minimize harm. It tool that helps our experts know the best “This kind of inventory opens up a lot of scours all of the data on head and neck way to use proton therapy. opportunities,” says Quon. “The data’s cancer patients treated in the Kimmel value is not just defined by what you want Cancer Center; charts radiation dose No one else is doing this because no one else to do now but also by the possibilities of distributions, toxicity and other data in has the technology to quantify and measure what we can do in the future.” 28 PROMISE & PROGRESS

Pediatrics A collaboration with Children’s National

Like adult patients, pediatric patients and what is the best approach to kill the When the National Cancer Institute receive radiation therapy as treatment for cancer and preserve everything else.” established four study groups to investigate a variety of cancers. Brain tumors are common childhood cancers in the late In fact, how to lessen the adverse effects the most common solid tumor in children 1970s, Johns Hopkins radiation oncologist of radiation has long been an area of and the cancer where most experts Moody Wharam was the only expert research among the Kimmel Cancer agree proton has the edge because of its appointed to two of the groups. From 1980 Center’s pediatric radiation oncologists. ability to so precisely spare surrounding to 1990, he served as director of the radia- normal cells. Although it is generally accepted that tion oncology committee of the Pediatric proton therapy provides benefit over Oncology Group, now known as the Chil- It is clear that every patient does not need other types of radiation therapy for dren’s Oncology Group, the world’s largest proton therapy. “It’s a necessary tool to pediatric patients, research studies are organization devoted exclusively to child- have to use at certain times, but not every lacking, and our experts understand hood and adolescent cancer research. time,” says DeWeese. “We look at each pa- better than most the important role of Wharam and Kimmel Cancer Center col- tient—pediatric and adult—individually to laboratory and clinical science in setting laborators were active participants in all of bring the best technology and treatment the standard of pediatric cancer care. the pivotal pediatric cancer research of the plan we have to bear against their cancer. We’ve been leaders for more than a time—research that led to dramatic We look at anatomy of where the tumor is half-century. increases in pediatric cancer survival rates.

Akila Viswanathan, M.D., M.P.H. (left) and Jeffrey Dome, M.D., Ph.D.

COLLABORATION Patients have access to the combined expertise of Children’s National and the Johns Hopkins Kimmel Cancer Center. THE SIDNEY KIMMEL COMPREHENSIVE CANCER CENTER at JOHNS HOPKINS 29

“The way we manage radiation therapy in “When children get exposed to radiation children today is based on what he did at a young age, they are at much higher through all those years of tireless work. risk of issues down the road when they That’s why we do research,” says DeWeese. are long-term survivors,” says Ladra. He is among a select number of radiation The cruel irony that the radiation treat- oncologists whose practice and research ments given to save the lives of young focus solely on pediatric cancers. “Our patients also has the potential to cause goal is to radiate what’s supposed to be harm continues to trouble radiation radiated and leave everything else alone. oncologists. Radiation to growing bones Proton therapy helps us do that.” and organs can impede normal develop- ment, and radiation to the brain, a The ability to better steer protons to common site of pediatric cancers, too Nanoparticles and the cancer and stop the beam means often results in impairments to learning Organoids developing brains, the heart, lungs and and other cognitive brain functions. Pediatric radiation oncologist Matthew growing bones can be better protected. Ladra is experimenting with protons, nanoparticles and organoids to deliver prom- Ladra says he has seen the benefits. He The ability to better ising new therapies to pediatric patients. recalls brain tumor patients he treated steer protons to with proton therapy who have none of One study uses nanoparticles—ultra-tiny the telltale signs of a brain tumor battle. the cancer and structures that can transport a cargo of “They have no cognitive issues. They are drugs and other cancer-fighting treatments growing normally. It’s very rewarding, stop the beam to tumors—to reset cells’ natural cancer- and the technology we have at Johns means developing fighting DNA. Ladra says that many pediatric cancers are missing a key tumor suppress- Hopkins is even better, and that means brains, the heart, ing gene, called P53, and the nanoparticles there are still advances that can be made,” transport the gene to cancer cells to put says Ladra. lungs and growing it back into action. bones can be Still, he knows that there is a difference “We use proton therapy to stun the tumor between anecdotal reports of benefits better protected. and open it up so we can infuse radiolabeled and scientific evidence. The latter is a key Reducing an p53 genes,” he says. The gene is already element that has been missing from the present in normal cells, so it only goes to conversation. unnecessary dose work in tumor cells. The radiolabel allows the scientists to see and track the gene inside Novel research, including a map of the is a good thing. cancer cells to confirm that if it turns on and helps shrink the tumor. brain that relates dose of radiation to im- In this long history of improving care for pact on specific areas of the brain, show- pediatric cancer patients, proton therapy Ladra also plans to collaborate with drug ing the maximum dose of radiation each is viewed as another major advance in discovery experts and other scientists to area of a young brain can tolerate without managing late effects of radiation therapy. study drug/proton combinations. In pediatric causing functional deficits, is providing Matthew Ladra, director of pediatric brain tumor research, he is excited about a information that other centers don’t radiation oncology, is eager to begin new model of discovery being used by have. It is revealing areas that will require proton therapy studies. Ladra was the radiation molecular scientist Sonia Franco. smaller doses of radiation but also others first radiation oncologist to earn a proton Tiny, organized spheres of human neural and that could safely tolerate larger doses. nerve cells about the size of a fly’s eye, therapy-specific fellowship, which he called organoids or minibrains, are providing completed at Massachusetts General The opportunity to study the benefits of an innovative way to research treatments of Hospital. This training led to a director- pediatric brain cancers. Franco is using them proton therapy is what attracted him to ship of the pediatric service at the to replicate how pediatric brain cancers the Kimmel Cancer Center. The Johns Provision Center for Proton Therapy in naturally grow and spread, and to study Hopkins National Proton Center is only Knoxville, Tennessee. more closely how these cancers respond to one of two in the country that has a radiation and drug treatment. In a precision dedicated pediatric facility and a proton Jen Holt, who also worked at the medicine approach, a minibrain could research program. Provision Center, joined Ladra as nurse be created as a stand-in for a patient by manager for the pediatric radiation implanting it with cells from the patient’s oncology program. brain cancer. 30 PROMISE & PROGRESS

“This is a truly visionary approach. growing organs. With its precision, the patient would most benefit from proton Research is the only way to get at proton beam offers the ability to get at therapy.” concrete evidence of the advantage of the cancer without harming these nearby using protons to treat children and to structures. As a result, experts believe it A teenage patient recently treated for show us how we can improve the care of may help patients avoid amputation. osteosarcoma that had spread, creating a kids moving forward,” says Holt. golf ball-sized tumor in the patient’s lung, Spinal tumors, cancers in the head and benefited from stereotactic ablative The dedicated pediatric oncology service neck, tumors that are close to other radiation. Surgery was not an option has its own team of experts—radiation organs—which in the small bodies of because of pre-existing damage to the oncologists and technicians, pediatric children can be many—and abdominal lung. Immunotherapy with drugs aimed nurses, including a nurse practitioner and pelvic tumors are also well-suited to at boosting the immune system to attack and nurse navigator, a child life specialist, proton therapy. the cancer was not keeping the cancer in a nutritionist, survivorship and family check, so the multispecialty team of counselors, and a pediatric anesthesiolo- For example, a toddler with a tumor doctors decided to use stereotactic gist, as very young patients often require sitting close to growth plates in the pelvis radiosurgery to go after the tumor in her some sedation during treatment. can be treated with proton therapy to lung. The tumor disappeared, and the protect the pelvic bones from radiation patient remains cancer-free. “The proton therapy technology is much damage that can cause the growth plates The combined treatment of immunother- better now, and we will have the most to close, resulting in growth issues and apy and stereotactic ablative radiation up-to-date proton facility, but expertise other problems later in life. In other can- allowed her to avoid more toxic is critical,” says DeWeese. “Like anything cers, such as Hodgkin lymphoma, that re- chemotherapy that is frequently ineffec- else, it has to be done well. We are learning quire radiation to the chest, proton tive against advanced osteosarcoma. now that there can be issues with proton therapy can protect the heart and lungs. For the teenager, who was about to begin therapy when not done correctly.” In other cases, another type of radiation high school, it was also a quality of life therapy may be preferable. issue. She didn’t want her hair to fall out, Proton therapy may also be a better op- and the radiation/immunotherapy tion for pediatric patients with sarcoma, “Proton therapy is an essential tool to combination worked better against her cancers of the bone and soft connective have at certain times, but it’s not the only cancer without altering her appearance. tissue. Sarcomas are particularly chal- tool,” says Ladra. “We look at anatomy of lenging to treat because they often occur where the tumor is and what we need to Working in collaboration with experts at in the vicinity of other vital anatomy and preserve and decide on case by case if the the Bloomberg~Kimmel Institute for Cancer Immunotherapy, our radiation oncologists uncovered evidence that cancer cells killed by radiation signal the immune system as they die, revealing their identity as a cancer cell and setting cancer-killing immune cells into action. Similar studies are planned combining immunotherapy and proton therapy.

“In a center with so much strength in every area of cancer research and ther- apy, we have more information to help inform our treatment decisions, and that leads to novel, patient-centered medicine and better outcomes,” says Holt. “There are so many things available here— comparative planning, specialized nursing care, multispecialty collaboration— COLLABORATION that are not available at other places. The “This shows how two nationally respected institutions came fact that we’re different from most of the together in a collaborative and proton centers out there is also what Kurt Newman, M.D. (left) and Theodore DeWeese, M.D. strategic way to change the face of pediatric cancer.” makes us better. Our patients get it, and their parents get it.” THE SIDNEY KIMMEL COMPREHENSIVE CANCER CENTER at JOHNS HOPKINS 31

CARE The dedicated pediatric oncology sevice has its own team of experts, including pediatric anesthesiologist Eugenie Heitmiller, M.D. (right).

The knowledge about the cancer being radiation oncology programs in the coun- Center’s pediatric oncology program. The treated must be equivalent to the proton try, and the increase in patient volume Kimmel Cancer Center’s pediatric cancer expertise, Viswanathan stresses. The promises to speed clinical discovery. program has consistently been ranked by multispecialty approach the Kimmel U.S. News & World Report as one of the top Cancer Center uses means each patient’s “It is another example of our strategic pediatric cancer programs in the country, care is informed by every specialist. Ra- focus to consistently partner with organ- and Children’s National was also ranked as diation oncologists, medical oncologists, izations in the region to bring high-qual- one of the top five children’s hospitals in pathologists, nurses, surgeons and other ity, accessible care to children and the country. The collaborations include experts work together to evaluate every families,” says Elizabeth Flury, Execu- joint clinical trials and research initiatives case and develop the best treatment plan. tive Vice President and Chief Strategy with the National Institutes of Health. “This multidisciplinary component is so Officer at Children’s National. “When we important because what really makes base our strategic decisions around “Working together through an integrated proton therapy at the Kimmel Cancer what’s best for the child, everyone wins. radiation oncology service—including re- Center special is what our experts bring This collaboration is a perfect example search—we are providing important new to it,” she says. of that thinking.” treatment options for kids fighting can- cer who live in the national capital area Unique Collaboration DeWeese believes it is a national model. or who travel here to take advantage of It is this kind of pioneering influence that “This shows how two nationally re- our joint expertise,” says Kurt Newman, earned the radiation oncology program spected institutions came together in a President and Chief Executive Officer of distinction as one of a select few in the na- collaborative and strategic way to change Children’s National. The joining of these tion with a long and proven track record the face of pediatric cancer care in the re- two leading programs marks a significant of excellence in treating pediatric cancers. gion and around the world,” he says. achievement in children’s health, he says.

In 2013, it helped pave the way for a Through the collaboration, patients have The collaboration represents the first collaboration with Children’s National. access to the combined expertise of Chil- pediatric radiation oncology program in It creates one of the largest pediatric dren’s National and the Kimmel Cancer the national capital region. DeWeese says

THE SIDNEY KIMMEL COMPREHENSIVE CANCER CENTER at JOHNS HOPKINS 33

CARE Zay Zay the Superhero Ezaylen’s “Zay Zay’s” mom, Phyllice, “I was very concerned at first,” says Phyllice, instinctively knew something serious was who was aware of the side effects radiation wrong when 2-year-old Zay Zay experi- treatment can have on young, growing enced persistent high fevers and constant children. “My husband convinced me we ear infections. Although her mother’s had to do it. The treatment would help make intuition was correct, she never imagined sure no cancer cells survived.” that the fevers and a protruding tummy she chalked up to a healthy appetite It’s a decision Phyllice has never regretted. were actually Wilms tumor, a type of “Johns Hopkins is awesome,” she says. pediatric kidney cancer. Two-year-old “Dr. Ladra is a great doctor. We had a good Zay Zay was diagnosed with stage III connection from the start, and everyone— cancer, and the tumor was occupying doctors, nurses, child life teachers— a shocking 90% of his kidney. stayed in constant communication with us, explaining the therapy and involving After chemotherapy and surgery to remove us every step of the way.” the diseased kidney, his Children’s National doctors recommended radiation therapy One year later, Zay Zay’s treatments appear as part of the treatment plan and referred to be working, she says. He still has more him to Matthew Ladra, director of pediatric chemotherapy ahead of him, but he has radiation oncology at the Johns Hopkins lived up to his love of superheroes and Kimmel Cancer Center at Sibley Memorial her nickname for him—little firecracker. Hospital. She says, “He’s small but powerful.” 34 PROMISE & PROGRESS

COLLABORATION The Johns Hopkins/Children’s National collaborative creates one of the largest pediatric radiation on- cology programs in the country.

From left: Lin Whetzel, B.S.N., R.N., Jennifer Holt, B.S.N., R.N., Matthew Ladra, M.D., M.P.H., Andrea Lattimore, B.S.N., R.N., Judy Tran, C.R.N.P

Theodore DeWeese, M.D.

Jean Wright, M.D. the dedicated, multispecialty team brings In addition to the cancer acumen of lead- ment program will advance combined the most advanced therapy and the high- ers in every field of cancer research and treatments with new targeted therapies, est level of safety and quality care for treatment, the National Proton Center has and a first-of-its-kind Cancer Invasion pediatric patients and families. at its disposal the brain trust of all of The and Metastasis Program, co-lead by Johns Hopkins University to lend their radiation oncologist Phuoc Tran, will “There are cases in which radiation is expertise and advance the application of study proton therapy, among other treat- the best way to enhance treatment for proton therapy alone and in combination ments, to transform the management of a young patient,” says Jeffrey Dome, with other cancer treatments. This advanced cancers. Oncology Division chief at Children’s progress is in line with everything else our National. “This collaboration is focused experts are doing to make cancer thera- “We can bring together so many things on finding the best strategies based pies work better for patients while also that are not available at other places. This in current research to integrate limiting toxicities. Targeted drug thera- wealth of expertise means we have more radiation therapy into a comprehensive pies, organ-sparing surgeries and less information coming, more people care regime.” toxic proton therapy all have this goal. informing decisions and solving prob- Built on Tradition So many things in cancer research have “We can bring together so many things their roots in the Kimmel Cancer Center. that are not available at other places. It is this convergence of expertise that makes the Johns Hopkins National This wealth of expertise means we have Proton Center stand out among others. Kimmel Cancer Center scientists and more information coming, more people clinicians bring expertise to all areas of informing decisions and solving problems, the cancer compendium and are among the undisputed leaders in cancer genet- and that leads to better outcomes for ics, epigenetics and immunotherapy. Add patients. We approach cancer from all to that Magnet nursing status recognition for quality of care, one of the first pro- angles. There is not one single preferred grams to study late effects of cancer solution. Sometimes it is a combination treatment and complete integration of cancer services across all Kimmel Cancer of therapies.” Center locations, and before its doors even open, the Johns Hopkins National Two specialized institutes will also sup- lems, and that leads to better outcomes Proton Center distinguishes itself among port our proton center. A new Transla- for patients,” says Akila Viswanathan. cancer centers and proton centers alike— tional Convergence Institute brings “We approach cancer from all angles. in the Baltimore/Washington region and doctors, nurses, astronomers, engineers, There is not one single preferred around the country. computer scientists, physicists, bioethi- solution. Sometimes it is a combination cists, biologists, materials scientists and of therapies.” To ensure quality of care and access to mathematicians together to work side by proton therapy among all of our sites, side to amass and apply their knowledge to Viswanathan says one of the most impor- radiation oncologist Daniel Song will cancer. They will solve complicated and tant collaborations will be with the lead regional chart rounds to discuss pa- vexing problems, build new technologies community of primary care providers tient cases across all Kimmel Cancer and consider out-of-the-box, creative who choose us to work with them to Center locations, including Sibley, Subur- new approaches that can only be found develop the optimal treatment plans for ban, Green Spring Station, Johns Hop- through this type of directed collabora- their patients. kins Bayview Medical Center and Johns tion. Hopkins Hospital. Jean Wright will “The Johns Hopkins National Proton Cen- oversee safety and quality across all loca- The Bloomberg~Kimmel Institute for ter is one of the few comprehensive proton tions. Clinical nurse specialist Jen Wei- Cancer Immunotherapy will help inte- centers in the world. We worka bridges all of the sites, overseeing grate proton therapy with immunother- will be doing research New on the Web intensive training for nurses to ensure apy, revolutionary new treatments that Watch our new video that has never been done about the Johns Hopkins the same standard of care exists at every activate the immune system to attack before,” says DeWeese. National Proton Center. hopkinscancer.org Kimmel Cancer Center location. cancers. A Drug Discovery and Develop- “It’s going to be a huge advance for the field.” NON-PROFIT U.S. POSTAGE PAID PERMIT #1608 BALTIMORE, MD

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