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Proton Therapy Is HereA New Standard of Care

PROMISE&PROGRESS

T H E S I D N E Y K I M M E L C O M P R E H E N S I V E C A N C E R C E N T E R AT J O H N S H O P K I N S

PROTON THERAPY IS HERE. The newJohns Hopkins National Proton Center atSibley Memorial Hospital is built upon along and rich tradition of excellence in radiation oncology, bringing nearly a half-century of cancer discovery and clinical progress to proton therapy.

It’s striking that this technology hasbeen around for more than 40 years buthas never really been tested in the research setting. This is what sets us apartfrom other centers. We ask the toughquestions because we are prepared to goafter the answers. With a dedicated proton research laboratory, our expertsare ready to do the hard work and gatherthe much-needed evidence to guide whenand how proton therapy is best used.

We waited until the technology wasright to bring proton therapy to JohnsHopkins, and when we did, we made it better, customizing it with our own inventions. Our proton therapy center will

Care.Collaboration. Innovation.

Promise & Progressis published by The Sidney Kimmel Comprehensive Cancer Center at Johns HopkinsOffice of Public AffairsBaltimore, Maryland410-955-1287

William G. Nelson, M.D., Ph.D.Director

Amy MoneDirector of Public Affairs

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Megan MattisPhotography Assistant

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For additional copies of this publication or further informationabout the Kimmel Cancer Center, please call 410-955-1287 or email [email protected].

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P&PT H E S I D N E Y K I M M E LC O M P R E H E N S I V E C A N C E R C E N T E R AT

J O H N S H O P K I N S

have the most advanced pencil beam,which paints tumors with cancer cell-killing energy layer by layer, staying withinthe boundaries of the tumor. The beam adjusts to differences throughout atumor to provide the right amount of energy to every different area of the tumor.

One size doesn’t fit all. Every patient,every cancer, is different, so we are ushering in the most advanced tumormonitoring that makes the already safeand targeted pencil beam patient-specificand even more tumor-specific. Advancedimaging and sophisticated data miningwill make complex comparisons of photon and proton therapies to ensureeach patient receives the therapy that isbest suited to his or her unique cancer.

We have the world’s leading expertsacross all disciplines and specialtiesworking in collaboration. This includes a collaboration with Children’s NationalHospital to create one of the largest pediatric radiation oncology programs inthe country. Few other centers can claimthis level of expertise. We know cancerand proton therapy. That is the JohnsHopkins difference. There are centers thatcan deliver proton therapy, and then thereare centers like ours that combine thehighest level of cancer care with scientific innovation to make sure thecancer medicine we deliver is the bestmedicine for each patient. Our new National Proton Center enhances our mis-sion of curing cancer and changing lives.

William G. Nelson, M.D., Ph.D.Marion I. Knott Professor and DirectorThe Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

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2 PROMISE & PROGRESS

Proton therapy may be a rare commodity,with less than 40 centers in the U.S., butthis level of expertise is even rarer. TheKimmel Cancer Center is among the veryfew that will combine cancer treatment excellence across all disciplines with proton therapy excellence.

“Patients and families need the team thatknows the most about the tumor. Youneed to know cancer, not just protontherapy. That is a differentiator for us,”says William Nelson, Director of theKimmel Cancer Center. “We bring thefull complement of Johns Hopkins expertise, spanning programs and departments, and nearly a half-century of

cancer discovery and clinical progress toproton therapy.”

Although this technology provides newopportunity to move cancer science andmedicine forward, not all proton ther-apy is created equal. We are not simplyusers and deliverers of proton therapy.Our scientists are also inventors,driving, testing and improving thetechnology to create a proton facilityunlike any other. Building upon alengthy history and strong foundationof pioneering discoveries in radiationtherapy, this center has the technologyto deliver the most advanced andpatient-centered care.

The translational ingenuity that mergeslaboratory discovery with clinical carethrives in the Kimmel Cancer Center. Itwas engaged throughout the planningand construction of our proton center. Asa result, it is one of the most comprehen-sive in the world, one of the very few sep-arate, dedicated rooms for research,pediatric patient care and adult patientcare. Proton therapy has raised manyquestions about for whom and how it isbest used. Our experts are answeringthose questions. They are providing the“why” and “when” of proton therapy.Despite commercial advertising to thecontrary, proton therapy is not new, andthe science is far from settled. “Althoughit has been around for a long time, it isvery much in its infancy in terms of ex-ploration and potential,” says AkilaViswanathan, interim director of the Department of Radiation Oncology andMolecular Radiation Sciences.

Technology without advanced and compassionate care is science alone. But technology in an environment of compas-sionate care, discovery and multispecialty collaboration focused on improving the lives of patients is cancer medicine.This is the hallmark of Johns Hopkins and the Kimmel CancerCenter, where innovation that exceeds the standard is thenorm. The result is an unsurpassed level of expertise in radiationoncology, molecular radiation sciences, physics, surgical oncology, medical oncology, cancer biology, engineering,quantitative sciences and more that Johns Hopkins Medicinebrings to proton therapy. This level of knowledge and multispecialty collaboration are fundamentally what set theJohns Hopkins National Proton Center apart from most otherproton centers across the U.S. Expertise matters because thereal value of proton therapy is in the specialists who developand use it.

Proton Therapy Is HereJohns Hopkins excellence issetting a new standard of care

COLLABORATION

Proton therapy hasraised many questionsabout for whom andhow it is best used. Our experts are helpinganswer those questions. They are providing the“why” and “when” ofproton therapy.

THE SIDNEY KIMMEL COMPREHENSIVE CANCER CENTER at JOHNS HOPKINS 3

HOW IT WORKS

Inside Our ProtonTherapy CenterThe proton is small, but it takes bigmachinery to generate and move thesesubatomic particles for treatment.

The SynchrotronA synchrotron is a type ofparticle accelerator used toaccelerate protons for use in proton therapy. It is26 feet in diameter andcomposed of a ring ofsmall magnets. Protons are injected into the ring andbegin traveling around the ring at great speeds,about 10 million times per second. Put another way,the speed of the protons is so fast, it could circlearound the earth five timesin one second. It is advanced technology overearlier generations of proton therapy because itcan produce beams of awide range of energies andreduces the risk of unnec-essary and unwanted radiation to the patient.

GantriesProtons travel downmagnetic devices intothe treatment rooms. A 360-degree, rotating,30-foot-diameter ironframework, called agantry, controls thespeed and direction of protons. It allowsradiation oncologists todirect the beam at anyangle and deliver the proton beam with pinpoint accuracy to a patient’s cancer.

Our center has four ofthese, with one gantrydedicated exclusively for pediatric patients and another for much-needed research.

Pencil Beam ScanningThis new technology funnelsthe protons into a narrowbeam—just a pencil tip’swidth—coming out of theproton therapy machinehundreds of times per second, scanning the tumorback and forth and up anddown, just to the edges ofthe tumor, to paint it layer bylayer with the cancer-killingproton beam. Our advancedtechnology is intensity mod-ulated, making it possible to deliver varying degrees of energy targeted to thespecific composition ofeach area of the tumor.

On-Board ImagingOurs will be among the first to have on-boardimaging. Plans for a CT Couch, invented bymedical physics Director John Wong in collaboration with Hitachi, will provide a built-inCT scanner that merges images of the cancer taken during treatment planning withones taken the day of treatment to verify thatthe tumor being treated has not changed ormoved. It facilitates precision treatment within one-tenth of 1 millimeter accuracy.

Respiratory GatingThe slightest motioncan cause tumors to move. Our protontherapy beam tracksdirectly to the tumor,stopping if the tumorshifts with the patient’sbreathing and startingup again when thebeam and tumor arealigned.


As a result, what truly is new in protontherapy is what the Johns Hopkins National Proton Center brings: the labo-ratory and clinical research to make itbetter and to advance its use as a tool ofprecision medicine. Our proton center isamong a select few academic centers inthe country—and the only in the region—doing research to determine in which situations this type of radiation treat-ment is the best option.

Proton therapy does not replace otherforms of radiation therapy. “We do wellwith all forms of radiation therapy, andthat’s something most other proton centers do not offer. That’s important because not every patient will need proton therapy,” says Viswanathan.

“Too much information is marketingdriven and not fact driven. Claims of clinical benefit are made with no scien-tific evidence to back them up. There isa lot we still do not know biologically,”says John Wong, director of medicalphysics. “At Johns Hopkins, we do itright.”

Radiation treatment, in all of its forms, isessentially a form of minimally invasivesurgery that replaces scalpels with precisely targeted radiation to get to can-cers, Wong explains. “The main reasonthere is no scientific evidence to supportmany of the claims of benefit is thatthere was no way to do research. Therewas no laboratory counterpart for whatwe do in the clinic,” he says. To solve that

problem, Wong invented the Small Ani-mal Radiation Research Platform(SARRP), a miniaturized version of themachines used to treat humans that is foranimal research and potentially otherlaboratory models. “SARRP provides arealistic model to study in the laboratorythe radiation treatment we give to patients, and this is critical to quantify-ing the benefits of one type of radiationtherapy over another and to finding thesafest and most effective way to treat patients,” he says.

Lack of research has been one of themost common criticisms of proton ther-apy. Although most experts agree that itsability to spare healthy cells by zeroingdirectly in on and stopping at the end oftumors makes proton therapy the radia-tion treatment of choice for pediatricand adult patients with tumors in thebrain or on or near the spinal cord, de-finitive research studies are lacking.Wong and collaborators are currentlyadapting SARRP to study proton therapy.One room in the proton center is outfit-ted specifically for research and will bededicated to the specific cellular, physicsand animal studies needed to refine anddefine who is best treated with protontherapy.

“What Johns Hopkins does so well is research to improve patient care,” saysTheodore DeWeese, Vice Dean for Clin-

ical Affairs and formerdirector of the Depart-ment of Radiation On-cology and MolecularRadiation Sciences.“We are one of the onlyproton centers that has

a whole room dedicated to thiskind ofresearch.”

Proton therapy expert Curtiland Devillesays it is the reason he came to JohnsHopkins. “I wanted to be in an academiccenter to be at the forefront of solvingissues and questions about proton ther-apy: What are the best indications forproton? Where can we increase benefit,

and where can we reduce toxicity?Where are we not getting such benefitand can let go? This is an area that islacking, and our center can begin to getto the answers.” The Johns Hopkins National Proton Center will be solvingthese unknowns and leading futureprogress, says Deville.

Radiation oncologist and gastrointestinalcancer expert Jeffrey Meyer was drawnto Johns Hopkins for the same reason.Meyer completed a fellowship in protontherapy before coming to the KimmelCancer Center and says that the Johns

Hopkins National Pro-ton Center is one of thefew addressing compli-cations associated withproton therapy, such asorgan movement andsensitivity to density

in organs. All of these questions andconcerns can be mitigated with research, he says.

“There are always going to be new tech-nologies. Expertise and the willingness todo research to know how to use it arecritical,” Meyer says. “It’s a great technol-ogy we want to take advantage of, but wehave to be smart about how we use it.”

Other proton experts, includingMatthew Ladra, a pediatric cancer specialist who directed a proton centerin Tennessee, and Jen Holt, a nurse fromthe same center, came to Johns Hopkinsand the Kimmel Cancer Center becauseof the combined excellence in researchand patient care.

“There are many aspects we still don’tknow and a lot of research opportunities.That’s something webring to the table, withthe goal to figure it allout and bridge thesegaps in knowledge,”

says Marikki Laiho, director of the Divi-sion of Molecular Radiation Sciences.

INNOVATION

Radiation treatment, in all of its forms, is essentially a form of minimally invasivesurgery that replacesscalpels with preciselytargeted radiation toget to cancers.

DEWEESE

MEYER

LAIHO


INNOVATIONHeng Li, Ph.D., Chief ProtonPhysicist, helps bring patientsthe most advanced radiationtherapy technologies, latesttechniques and innovativetreatments.

COLLABORATIONAt left, John Wong, M.D. director ofmedical physics. The Johns Hopkins National Proton Center build upon alengthy history of pioneering discoveries in radiation therapy and offers the technology to deliver the most advanced and patient-centered care.


“We do well with all formsof radiation therapy, andthat’s something mostother proton centers don’toffer. That’s important because not every patientwill need proton therapy.”

INNOVATIONAkila Viswanathan, M.D., M.P.H., Interim Director of Radiation Oncologyand Molecular Radiation Sciences,says although proton therapy hasbeen around for a long time, it is verymuch in its infancy in terms of explo-ration and potential. What truly is newis the research and multispecialty collaboration the Johns Hopkins National Proton Center brings.


Photons and ProtonsRadiation oncology is unique in that it isthe only specialty that makes its ownmedicine. Radiation treatments deliv-ered by machines essentially come in oneof two forms: photons or protons. Al-though every radiation oncology expertrecognizes that photon therapy and proton therapy are different, no one hasstudied them at the level proposed byour experts.

"We will be able to leverage our extraor-dinary talent in order to advance thefield," says Viswanathan.

Long-term research data made possiblethrough Wong’s SARRP technology makeit possible to begin comparative pho-ton/proton studies almost immediately.

“This will give never-before-seen insightsinto the actual biologic effects of proton,”she says.

Photons are a higher-energy version ofthe same X-rays used for diagnostic im-aging. These high-energy X-rays can bepointed at a part of the body where a cancer is located and, through a series ofinteractions inside of the body, break theDNA inside the cancer cell, rendering itunable to repair or copy itself. As a result, the cancer cell dies.

Proton therapy is called heavy ion ther-apy. It essentially kills cancer in the sameway—breaking the DNA—but it usescharged particles directly rather than X-rays to kill cancer. Many experts believe that protons do a better job ofbreaking the DNA than photons, and thisis an area Laiho is eager to explore.

“Protons damage DNA directly, and thattype of damage is harder for cells to repair,” says Laiho, whose research focuses on understanding the benefit of radiation therapy with drugs that furthercripple cells’ ability to repair DNA dam-age. “If we combine proton therapy withdrugs that inhibit DNA repair pathways,the interaction will likely be greater thanwhat we see with photons.”

One key difference between X-ray or photon radiation therapy and protontherapy is already known. It goes to thevery core of why proton therapy is bene-ficial. It’s not that it kills cancer better;it’s that it damages normal cells less.Photons pass through the cancer and outthe other side, so on this exit, they hitnormal cells and tissue. Proton therapy,on the other hand, stops at the tumor.There is no exit dose. “Conventionalphoton radiation therapy and protontherapy cure tumors at the same rate,”explains Viswanathan. “The side effectsthey can cause are similar, but with proton, less dose goes to normal cells,and that’s the benefit.”

What Viswanathan describes is technicallyknown as the Bragg peak. As protonstravel through the body, most of the energy is reserved and released wherethe protons stop—in the tumor. Photonsrelease energy along the entire path theytravel. This fundamental difference iswhat makes proton therapy preferentialfor certain tumors. If vital organs or structures are along the path the radiation travels, protons cause less damage to them.

It can reduce excess radiation to normalcells and to vital structures and organs byabout 1.5 to three times, Viswanathansays. But at two times the cost of photonradiation, clinical data to prove proton’sbenefit over photon radiation is essentialto moving the technology forward.

DeWeese says photons and protons bothhave their place in radiation therapy,and that’s why advanced knowledge ofthe field is so important. One area, hesays, where the benefit has clearly beendemonstrated is pediatric patients and

tumors in the brain, spine and when thecancer is located close to vital organs,like the heart. Head and neck cancers,tumors located at the base of the skullwhere nerves come out, breast cancersnear the heart, lung cancers in themiddle of chest or near the esophagus,certain pancreas and abdominal tumors—essentially any cancer locatedin or around complicated anatomy thatneeds to be shielded from radiation—may be better suited for proton therapy.When combined with lumpectomy, pro-ton therapy could potentially improvebreast-conserving treatments. However,all of these benefits must be proven definitively through clinical trials, DeWeese says, adding that these studiesmay show cancers that can be treatedjust as effectively with less expensivetherapies, but they will also reveal whenproton is the preferable choice.

Prostate canceris a cancer wheremany questionsremain. Protontherapy has beenused frequently

WEB EXCLUSIVEListen to On Target with Dr. Akila Viswanathan, Interim Director of RadiationOncology and MolecularRadiation Sciences:http://bit.ly/2TD58vr

INNOVATION

As protons travelthrough the body,most of the energy is reserved and released where theprotons stop—in the tumor. Photons release energy alongthe entire path theytravel.

BRAGG PEAKAs protons travelthrough the body,most of the energy isreserved and releasedwhere the protonsstop—in the tumor.

“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.”

Curtiland Deville Jr., M.D.,Associate Director of theJohns Hopkins National Proton Center.


to treat the cancer. National trials are on-going, but currently, all available evidenceshows that both types of radiation therapyhave equal benefit.

“The fundamental issue with proton forprostate is do we have a clinically mean-ingful benefit that justifies its increasedcost?” asks Deville. Generally, he says, pho-ton and proton therapy provide compara-ble results for prostate cancer, but photontherapy is a less expensive treatment.

“I am a prostate expert,” says DeWeese.“I’m not sure it’s a substantial advantagefor this cancer. But that’s OK. Thesekinds of studies have to be done to deter-mine when other forms of radiation ther-apy will work just as well at a lower cost.”

Deville would like to study proton ther-apy in younger men diagnosed withprostate cancer, particularly those whohave a recurrence after surgery. who donot want to have surgery. Young patientsare at greatest risk of developing radia-tion-induced secondary cancers later inlife, and proton therapy could preventthese toxicities. Other functional charac-teristics could also indicate prostate can-cer patients who may develop fewerquality of life-impacting side effects withproton therapy. Patients who have re-ceived radiation and could benefit fromadditional treatment, or re-radiation, isanother circumstance where the preci-sion of proton offers an advantage in var-ious types of cancer. There may be patients who, in the past, would havebeen excluded from radiation therapythat could be beneficial against their can-cers because of toxicities, says Deville.

On the other hand, photon, with itsmore scattered energy, may be the bet-ter choice for tumors that are not so precisely located but rather dispersedthroughout an area of the body ororgan. These types of comparative stud-ies will be standard practice at theJohns Hopkins National Proton Center.

The lack of comparative studies betweenphoton and proton therapy was a primary

reason DeWeese and Viswanathan set up the proton center to have an unparal-leled emphasis on research.

One important areaof research focus

will be relative biological effectiveness,or RBE, how much more effective is pro-ton therapy compared to photon radia-tion therapy. They want to know whatdoses of each type of radiation therapyare required to produce the same clinicaleffect. Just as important, they need toconfirm that the prescribed dose is actu-ally being delivered and going where theyexpect it to go.

Linear energy transfer, or LET, is the density at which the energy is depositedalong the path to the tumor and in the tumor. Protons travelmore quickly en route to the tumor, depositinglittle energy or lowerLET. The protons slowinside the tumor, andthat is where the highestdensity of cancer cell-killing energy is trans-ferred or deposited,explains physicist ToddMcNutt, who is part ofthe expert team thatmakes the complex cal-culations that maximize damage to cancer and minimize risk to healthy organs and tissue. The region where the energy is the highest is right at theedge of the tumor, he says. This is whyexpertise is so critical. “If you don’t get it right, the highest LET may hit outsidethe tumor, and if there is a narrowboundary between the tumor and a critical organ or structure, the patientmay be harmed.”

RBE helps researcherslearn what doses of eachtype of radiation therapyare required to producethe same clinical effect.

Linear energy transfer, or LET, is the density of energy deposited along the path to the tumor and in the tumor. Protons travel more quickly en route to the tumor, depositing little energy or lower LET.

CONTINUED ON PAGE 12.

CARE

Urologic Cancers and SarcomaCurtiland Deville specializes in thetreatment of urologic cancers, such asprostate cancer, and soft tissue sarcoma, a rare cancer of the soft tissues of the body.

The fundamental benefit of protontherapy is that it has no exit dose, Devillesays, and this reduces unnecessary ra-diation exposure to surrounding normal,healthy tissues. Proton therapy also pro-vides the potential to treat in challengingclinical scenarios. When soft tissue sar-comas in the arms or legs recur, the pa-tient may be spared an amputation byundergoing a repeat course of radiationallowing for limb-sparing surgery.

Deville also published the first clin-ical studies on the use of proton ther-apy for prostate cancer after surgery.“This is an exciting area, particularly for young men who have undergone sur-gery for their prostate cancer and experience recurrence in the prostatebed where the prostate was located,”says Deville. When treating the prostate, the development of an in-jectable, absorbable “hydrogel” spacer, protects adjacent bowel andrectum during treatment.

Seminoma is a rare but highly cur-able form of testicular cancer that typ-ically affects younger men. Radiationmay be used after surgery to reduce the risk of or treat recurrence. Protontherapy may reduce the risk of secondcancers benefiting these often young patients, says Deville.

“I was drawn to the Kimmel Cancer Center because of its clinical and researchexpertise and patient-centered ap-proach,” says Deville. “The goal is alwaysto leverage this wealth of experience,bring this expertise to the community, andimprove the treatment of patients.”

He likes being based at Sibley, which brings the expertise and re-sources of a major academic univer-sity to a community environment. He is excited about partnering with otherdoctors in the community and other local institutions, such as the UnitedMedical Center, Howard University and Children’s National. “These clinicalcollaborations enhance our impact onpatients in the broader national capitalregion and beyond, providing conven-ient access to unique care and worldclass treatments, such as the most ad-vanced radiation therapies and clinicalinnovations.”


planning and delivery of proton therapy.Respiratory gating technology tracks theproton beam to movement of the tumor.Our experts helped invent and developthese technologies.

Pencil Beam and Other Advanced Tech-nologies: It is one of just a few incorporatingthe latest pencil beam delivery that virtuallypaints tumors with cancer cell-killing radia-tion while sparing surrounding normal tissue.

Research Center: It is the only academicproton therapy center in the region and oneof just a few in the world where much-needed research studies will be performed todecipher basic biological mechanisms andhelp set the standard of care for proton therapy now and for the future.

Precision Medicine: Our experts take aunique multidisciplinary and precision

medicine approach that brings together allspecialists and experts to work with patientsto develop individualized, detailed treatmentplans specifically suited to each patient.

Local, National and International: The location of our proton center at Sibley Memorial Hospital in Washington, D.C.,allows us to continue to bring the mostadvanced cancer care to patients living in theregion, while also providing care to patientsacross the U.S. and around the world.

Access for All: Collaboration among theJohns Hopkins Kimmel Cancer Center, Children’s National Hospital and HowardUniversity ensures advanced cancer careto patients of all ages, including childrenand young adults, and the most underserved communities in the region.

The Johns Hopkins National Proton Center What Sets Us Apart

Unparalleled Expertise: Since opening asone of the first comprehensive cancer centers in the nation, the Johns HopkinsKimmel Cancer Center and its experts haveled cancer research, deciphering the causesof cancer and advancing care for the mostcomplex cancer cases. This level of expertisecontinues with our proton therapy center,which will be directed by the leading radiationoncology and medical physics experts in theworld.

Largest and Most Advanced: Our 80,000-square-foot facility is one of the largest andmost advanced facilities in the world, withfour treatment gantries and dedicated research and pediatric-specific space.

Imaging Couch and Respiratory Gating:It is the only proton center with CT imagingintegrated with treatment to ensurethe most accurate and precise treatment

THE SIDNEY KIMMEL COMPREHENSIVE CANCER CENTER at JOHNS HOPKINS 1 1

Johns Hopkins National Proton Center Med-ical Director Christina Tsien, a leading brainand central nervous system tumor expert,brings a wealth of expertise to her new role.

Tsien comes to Johns Hopkins fromWashington University School of Medicinein St. Louis, Missouri, where she was chief ofthe Central Nervous System Service, directorof clinical research for radiation oncology,and co-medical director of stereotactic radio-surgery and the gamma knife center.

Her mission for the Johns Hopkins Na-tional Proton Center is to ensure patients re-ceive outstanding individualized care,provide the very best training opportunitiesfor faculty and staff members, and maintainan active clinical and translational researchprogram.

“We are bringing world-class cancer careand cutting-edge research to patients hereand around the world,” says Tsien.

The Johns Hopkins National Proton Cen-ter is committed to providing pediatric andadult patient-centered clinical and researchprograms, she says. “In collaboration withChildren’s National, we will have a strongfocus on improving outcomes for pediatricpatients and reducing short-term and long-term treatment side effects,” says Tsien. Thisincludes using proton therapy to reducetreatment-related impact on growth and cog-nition, and the risk of secondary cancers laterin life, she says.

“For adults, the potential impact of protontherapy can also be substantial,” Tsien says.“Radiation therapy is an integral componentof cancer care, with over half of all patientsdiagnosed with cancer receiving radiation

therapy as part of their treatment.”Tsien and colleagues are excited by the

possibilities of using proton technology to im-prove radiation treatment of tumors next tocritical organs. Tsien notes that the NationalProton Center has state-of-the-art pencilbeam technology with image guidance, whichaffords physicians the ability to deliver highlyprecise and conformal proton therapy.

“Johns Hopkins physicians are world-renowned experts in the treatment of cancer,and they are committed to clinical trials andtranslational research to improve the qualityof life and outcomes for cancer patients, pro-viding evidence on how proton therapy canreduce long-term radiation side effects,” saysTsien. This includes protecting the heart forbreast cancer patients and reducing short-and long-term effects on normal swallowing,dry mouth, taste changes and weight loss inhead and neck patients, she says.

“Treatment of brain tumors will also be akey area of cancer care progress because ofthe potential to preserve vision, hearing,memory, and vital brain stem, pituitary andneuro-cognitive function,” says Tsien.

Tsien adds that proton therapy is an excit-ing opportunity for patients who otherwisemight be excluded from radiation therapybecause of prior radiation treatments.

“Proton therapy is an incredibly complexand precise tool, and there is still much to bedone for experts to harness its full potential,”she says. “We are working to develop ad-vanced imaging techniques to monitor treat-ment changes in real time, allowing us toadapt radiation treatment plans. We arebuilding better motion management tools,and we want to improve our understandingof radiation tumor biology to further increasethe effectiveness of proton therapy in combi-nation with systemic therapies.”

Tsien is eager to study proton therapy incombination with immunotherapy, targeteddrug therapies and systemic therapy — treat-ments that work to zero in on specific molec-ular alterations that drive cancer growth andspread.

“Combining proton therapy with othercancer treatments may help prevent cancerrecurrence, and this will be an active area ofpreclinical and clinical translational researchin the Johns Hopkins National Proton Cen-ter,” Tsien says. “Our purpose is to figure outhow to improve cancer survival, and oftenthe best way to do that is to use different can-cer therapies in combination to deliver highradiation doses to the tumor while minimiz-

ing dose to the surrounding normal tissues.” Among the strategies Tsien wants to re-

search is the use of ultrafast flash radiationtherapy with proton therapy to maintain highdoses of radiation to tumors while reducingthe dose to normal tissues. “This would ulti-mately enable us to substantially shorten thelength of treatment from several weeks toseveral days,” she says.

Radiation oncologists now have many dif-ferent cancer-fighting tools at their disposal,and Tsien stresses the importance of select-ing the right treatment plan for each patient.“Proton therapy will not be suitable foreveryone, and we are committed to ensuringpatients receive the best and most suitabletreatment,” says Tsien.

“One of the most rewarding things for meis the opportunity to work as a treatmentteam, to give every patient a second look tomake sure nothing has been missed and thatwe’ve explored every possible avenue andevery treatment option,” she says. “We needto identify patients who will benefit the mostfrom proton therapy and learn more about itsimpact on tumors and normal tissues. Wealso need to go into the laboratory to revealthe cellular mechanisms that can answerquestions like why a specific treatment maywork in one patient but not in another.”

Tsien says Johns Hopkins National ProtonCenter experts will work closely with col-leagues throughout the Johns Hopkins sys-tem as well as with colleagues at otherorganizations such as the National Institutesof Health. “We are aiming to provide the verybest patient care and to be on the forefront ofinnovative proton research,” she says.

As Tsien looks ahead, she also thinks backto her own diagnosis as a young medical stu-dent with a rare type of sarcoma. It led her topursue a career in radiation oncology. Protontherapy was not available at that time, andher experience reminds her of the continuingneed to advance cancer therapies. She under-stands cancer on a professional and personallevel and chose to come to the Johns HopkinsNational Proton Center, she says, because ofthe opportunities uniquely set up to pursuenovel clinical and laboratory studies usingstate-of-the-art proton therapy with the aimof transforming patient care.

“I am excited to be here,” says Tsien, “andwhat I’m most excited about is helping pa-tients everywhere get the best care, and thatmeans we are always looking to the futureand always moving forward. Our goal is toeliminate cancer.”

LEADING THE WAY

Meet National ProtonCenter Medical Director Christina Tsien


Deville is among Kimmel Cancer Centerexperts who are eager to collaborate withMcNutt and use his Oncospace data min-ing system to track and compare toxicitieswith photon and proton therapy to de-velop a precision medicine approach. Hesays it could help identify prostate cancerpatients who would benefit from protontherapy.

“This is the right direction for an aca-demic proton center like ours. High-level evidence has been lacking. Kimmel Cancer Center experts can bring their expertise into the research realm, and 10years from now, we’ll have these answersto set the standards of care,” says Deville.

Better from the StartEven before the research begins, DeWeese and Viswanathan are confidentthat the Johns Hopkins National ProtonCenter is poised to deliver unprece-dented care. Our 80,000-square-foot pro-ton center is one of the largest in thecountry and has four gantries—the large,sphere-shaped structures that housethe equipment used to deliver protontherapy to patients. The gantry rotates around the patient, delivering theproton beam at any angle necessary totarget the cancer. Unique features, including the pencil beam, a tumor trackingsystem that allows the beam to adjust totumor movement, in-room imaging via aCT Couch and the Oncospace data min-ing system, are all unique to the Kimmel

Cancer Center and make the proton therapywe provide the safest and most advancedavailable.

How we deliver radiation therapy at theKimmel Cancer Center is already a stepabove most other places, DeWeese says. Advanced expertise has kept radiationdelivery very focused, conforming to thetumors, and allowed our doctors and scientists to make every type of radiationtherapy technology work the best for patients while minimizing harm.

To that point, DeWeese recalls a patienthe treated as a resident who poignantly illustrates the tradition for patient-centered care and ingenuity that remainthe heartbeat of the department.

Ana Kiess often treats cancers that occuramid confined spaces in the proximity of thebrain, eyes and other vital anatomy. She plans to explore proton therapy for thetreatment of salivary gland and skull-basedtumors to spare the brain stem, brain andoptic structures from radiation. The precisionof proton therapy and the ability to stop thebeam at the tumor will provide new opportunities to cure patients with advancedcancers, she says. In sinus and nasal cancers, calculating radiation dose is difficultbecause of the potential density changes.

“The patient may have clear sinuses astreatment begins that become filled withmucus before the end of treatment,” she says.

As a result, these patients require complextreatment planning, replanning and dose calculations to account for these dynamicchanges. She will be collaborating with Oncospace (see page 25.) inventor ToddMcNutt and others to use data to help cre-ate sophisticated advanced planning forthese patients. Kiess is excited about proton therapy clinical trials for patients with theseless common cancers.

“Through clinical trials, we learn from eachpatient, improving the understanding of tox-icities and ways to improve treatment," shesays.

CARE

Head and Neck Cancers

CONTINUED FROM PAGE 9.

In 1990, he was working with a former faculty member, the late MoodyWharam, to treat a young patient withthe rare occurrence of an eye cancercalled retinoblastoma in both eyes. With-out extraordinary measures, the youngboy was destined to lose vision in botheyes, DeWeese says. The only way to preserve the function of one eye was todeliver radiation so precisely that it woulddestroy the cancer without harming theanatomy of his eye.

The treatment was so complex, includingthe construction of a special device forthe patient’s eye, that DeWeese recallscoming in every morning for weeks at 6a.m. to set up for the patient’s treatment.Technologies to perform this type of precise radiation treatment, like protontherapy and stereotactic ablative radio-surgery, had not yet been developed, soDeWeese and Wharam fashioned theirown way to get radiation to the cancerand protect the eye. It worked, and in2017, the patient graduated from collegewith an engineering degree. He sentWharam and DeWeese a family phototaken at his graduation. DeWeese won-ders how different that family photomight have been if they had not gone tosuch lengths to save the patient’s visionin one eye.

“I can’t think of too many places at thetime that had the team to innovate thistype of care to save this child’s eye,” saysDeWeese, adding that this remains thetype of care that every patient who comesto the Kimmel Cancer Center receives.

This dedication to patients and the abilityto successfully plan and deliver such acomplex treatment exemplifies the differ-ence between radiation therapy at JohnsHopkins, including proton therapy, andradiation therapy most everywhere else.

It is these “extra lengths” that make ourproton center unique from the start.

Our proton center also has the most up-to-date pencil beam technology, whichonly recently became available. The pencil beam paints tumors with cancercell-killing energy layer by layer, stayingwithin the boundaries of cancer. Thetechnology is so advanced that it is ableto modulate intensity, delivering varyingdegrees of energy based on the specificmakeup of the tumor. Instead of the sameenergy being deposited throughout thetumor, our pencil beam adjusts to differ-ences throughout a tumor to provide theright amount of energy to every differentarea of the tumor.

Collaboration among Kimmel CancerCenter molecular radiation scientists andthe manufacturer of our proton therapysystem means our National Proton Center will usher more advanced tumormonitoring that makes the already safeand targeted pencil beam patient-specificand even more tumor-specific. Onemethod uses molecular monitoring toevaluate the tumor and adapt radiationtreatment to each individual patient. Molecular imaging allows doctors to differentiate cancer cells from scar tissueor other ambiguous lesions and better define the anatomy of the tumor and itsresponse to radiation treatment.

“When protons interact with human tissue, they produce things like oxygen ina different molecular state. We can use a

type of imaging called a PET scan to seethat and know exactly where radiationwas applied that minute. Based on whatwe see, we may deliver the dose on thatday in one way, and the next day, use aslightly different dose or angle of treat-ment or energy,” says DeWeese.

Wong worked with proton therapy devel-oper Hitachi to integrate another inven-tion, called respiratory gating, that tracksmotion in the lung and stops the pencilbeam if the beam and tumor lose align-ment due to motion caused when patients breathe.

“The machine only fires when the beamis in the right place,” says Wong. “If thetumor moves, the machine automaticallystops. The beam works when it is linedup and stops when it is not lined up.We’re the first to have it.”

Wong says the studies needed for FDAapproval of the gating technology will bedone at our National Proton Center.

Another technology being studied byWong and physicist Kai Ding further

buffers vital organsfrom the energy of theproton beam. Some tu-mors sit right next tocritical structures, andproviding a buffer be-tween the organ and

the tumor could make it safe to deliverhigher doses of radiation to the tumor,Wong says.

Ding received funding from the NationalCancer Institute to study image-guidedinjection of a spacer gel to push tumorsaway from radiation-sensitive organs. Forexample, in pancreas cancer, the spacergel could be used to push the tumor awayfrom a section of the small intestinecalled the duodenum. Protecting nearbyorgans would permit higher doses of ra-diation to the tumor. Studies of the spacergel have already begun in photon radia-tion therapy and will begin in protonwhen the center opens.

DING

COLLABORATION

Advanced expertisehas kept radiation delivery very focused,conforming to the tumors, and allowedour doctors and scientists to makeevery type of radiationtherapy technologywork the best for patients while minimizing harm.




1973: Johns Hopkins is among the first tobe designated a Comprehensive CancerCenter by the National Cancer Institute.Medical oncologists, radiation oncologists,surgeons, oncology nurses, researchersand other specialists work together to advance cancer treatment and research.

Radiation oncology broke off from the Department of Radiology and RadiologicalSciences and joined forces with the Department of Oncology to make progressagainst a growing cancer epidemic.

1976: A specialty cancer program for pedi-atric patients is established. The NationalCancer Institute appoints Kimmel CancerCenter radiation oncologist to two nationalstudy groups investigating childhood cancer.

1977: Johns Hopkins’ program was viewed as one of the few strong academicprograms in radiation oncology in the U.S.This expertise attracted so many patients,the radiation oncology clinic had to expandto twice its original size to accommodatethe growing patient load.

1980: A Kimmel Cancer Center radiation oncologist is named director of the radiation oncology committee of the Pediatric Oncology Group, a position heheld for 10 years. He was among the firstto study toxicities and late effects of radiation therapy on pediatric patients.

1986: Our radiation oncology experts become the first in the region to performstereotactic brain surgery, a computer-generated surgery performed withoutknives, in order to destroy deep-seated tumors and blood vessel malformations in the brain.

1989: A new treatment delivers radioactive“seeds” into the airways, extending life forinoperable lung cancer patients. The sametype of therapy, now known as brachyther-apy, is used to treat prostate and gyneco-logic cancers.

1993: Investigators discover thatchemotherapy and radiation therapy administered prior to surgery improve success rates in some cancer patients.

1994: The Kimmel Cancer Center becomesone of the first in the nation to use a 3D radiation simulation for more preciselyplanned radiation therapy.

2001: A combined chemotherapy/radiationregimen preserves the voice box for manylaryngeal cancer patients with success ratesequal to surgical removal of the voice boxand significant improvement in quality of life.

2003: The Department of Radiation Oncology and Molecular Radiation Sciences is established.

2004: The Intensity Modulated RadiationTherapy Program began to deliver high-precision radiation that conforms to thethree-dimensional shapes of tumors anddelivers higher and well-defined doses of radiation to tumors, and even specificareas within tumors, while minimizing radiation to surrounding normal tissue.

2005: Miniature versions of the equipmentused to treat patients are created to performnever-before-done animal research models.These models allow researchers to studythe best ways to target radiation-basedtreatments to tumors and, at the same time,prevent damage to normal cells.

2006: Research reveals that lower doses of radiation may kill more cancer cells byeluding a protein called ATM, a damage detection mechanism for cancer cells.

Science Watch newsletter dubs the KimmelCancer Center a “cancer research power-house,” as its research is the most oftencited in all of cancer research worldwide.

2007: The stereotactic body radiation ther-apy program starts. This knifeless surgeryuses highly focused beams of radiation to ablate tumors.

2008: Molecular Radiation Sciences researchaccelerated to decipher the biology of DNAdamage response to radiation therapy andhow cells sense and repair this damage.

Research showed that men whose tumorsrecurred after prostate cancer surgery arethree times more likely to survive their disease long term if they underwent radiation therapy within two years of the recurrence.

The Path to ProtonMilestones in Radiation Oncology

Excellence in proton therapy emanates from excellence in all areasof radiation oncology. Our National Proton Center is built upon astrong history of breakthrough discoveries and scientific ingenuity.


2009: A computer-assisted version ofbrachytherapy, a prostate cancer therapythat uses radioactive seeds inserted in theprostate to kill cancer cells, is developed.The innovation allows for more preciseplacement of seeds. An even more preciseversion followed, using an MRI-assisted ro-botic needle to accurately insert the seeds.

2010: A technique to keep normal and cancerous tissue surgically removed fromthe prostate alive and functioning for up toa week is developed to allow investigatorsto test anticancer therapies on live tissue.

2010: Sibley Memorial Hospital in Washington, D.C., becomes part of theJohns Hopkins Health System.

2011: Our experts led the first-ever, in-depth,scientifically based safety analysis of radiation oncology and reported that a combination of approximately six commonquality assurance measures could haveprevented more than 90 percent of the po-tential incidents.

2012: A new, never-described compoundknown as BMH-21 destroyed critical communication between cancer cells andthe POLI pathway, necessary for cancercell survival.

2013: The Johns Hopkins application tobuild the largest and one of the most advanced proton therapy centers in thecountry is approved.

2014: An interdisciplinary research collaboration reveals that testosterone, a hormone prostate cancer cells need tosurvive, can also form breaks in the DNAthat would make cancer cells more vulner-able to treatment with radiation therapy.

2015: A unique collaboration between our Department of Radiation Oncology atSibley and Children’s National pediatriccancer center results in the first dedicatedpediatric radiation oncology program in thenational capital region. It brings togetherpediatric medical and surgical oncology experts from Children’s National and pedi-atric radiation oncology experts from theKimmel Cancer Center to provide compre-hensive pediatric cancer care, includingclinical trials, to patients in the region.

Stereotactic radiotherapy is shown to augment immune response in pancreaticcancer patients.

2015: The Kimmel Cancer Center at Sibleypartners with United Medical Center andHoward University to bring cancer care tothe most underserved Washington, D.C.,neighborhoods.

2016: The Kimmel Cancer Center at SibleyMemorial Hospital opens adding medicaloncology and surgical oncology to the already established and growing radiationoncology program. The 36,000-square-footfacility brings patients the most advancedradiation therapy technologies, latest techniques and innovative treatments—the same techniques and technologies usedthroughout the Johns Hopkins Kimmel Cancer Center.

2017: A pioneering new therapy uses CT- and MRI-guided brachytherapy to treat cervical cancer and other gynecologiccancers.

2018: U.S. News & World Reportcontinues to rank the Kimmel Cancer Center as one of the top cancer hospitalsin the nation and the top-ranked center in the mid-Atlantic region. Our pediatric oncology program is also ranked amongthe top five in the nation.

2019: The Johns Hopkins National ProtonCenter opens, bringing the most advancedproton technology, expertise and researchto the region.

On the WebWhat is Proton Therapy?Watch our informativeintroduction to protontherapy – the precisionradiation therapy:http://bit.ly/2TD58vr


COLLABORATION

A New Approach forAdvanced CancersPatients like David with advanced cancers are benefitingfrom a new, first-of-its-kind Cancer Invasion and MetastasisProgram, co-directed by radiation oncologist Phuoc Tran.The new research tackles cancer spread head on—the causeof more than 90% of cancer deaths.

Tran believes cutting off the metastatic or spreading cancercells 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 havehistorically been excluded, and combining chemotherapy, targeted drug therapies, surgery and radiation therapy, including proton therapy, to transform the management of advanced cancers.


The InventorAffable and brilliant, Wong’s energy and

his excitement for thefield are infectious. Hemoves between meet-ings with young up-and-coming physicists in hisoffice to the stairwell ashe scurries to the treat-ment areas to see his in-

ventions in practice and interacts withclinicians who can describe existing short-falls. Along the path, he stops to talk to fac-ulty members, nurses, technicians,residents and fellows. He is always think-ing about how he can make radiation ther-apy better. More impressively, he hasturned these ideas into revolutionary ad-vances in the field of radiation oncologyand molecular radiation sciences.

“It’s great to be paid to sit and think,” hejokes.

He rarely believes a new technology isadequate “out of the box,” and protontherapy was no exception. His inventionsmake existing technologies better, saferand more precise. He epitomizes the intangible component so essential to pro-

ton therapy, or any radiation therapy, forthat matter. It is the expertise, experienceand in-depth knowledge that allow himto optimize a new technology to workbetter for the radiation oncologists,physicists, nurses and technicians whouse it and—his main goal—to advance thecare of patients.

Most places acquire proton therapy bycontracting someone else to build it forthem. Wong and his Kimmel Cancer Center colleagues took a different approach, partnering with manufacturerHitachi to design and build a one-of-a-kind proton therapy system that exceeds every other proton center in itsscope, size and capability.

“We have always been innovators in theKimmel Cancer Center. There are fewplaces like us, but this is how leading institutions like Johns Hopkins should bedriving the development of technology.When we see a clinical problem, we solveit ourselves,” says Wong. “I look for log-ical ways to make equipment work better,which allows researchers to dig deeperand move faster so they can get improvedtreatments to patients.”

Most of Wong’s inventions over morethan three decades are centered on imag-ing that makes sure the potent radiationbeam hits its intended cancer target.

The protection of normal tissue and organs is at the center of most everythingour experts do in treating patients withradiation therapy. There is no questionthat radiation kills cancer cells. Researchers have understood that since1896. At issue is how it can be used to killcancer without harming normal cells toprevent toxic side effects at the time oftreatment, particularly for pediatric andyoung adult patients, down the road,when excess doses of radiation can resultin long-term side effects or cause secondcancers to develop.

The ability to direct the beam to a tumor,and only the tumor, is the advantage of

proton therapy over the more scatteredphoton beam. However, the beam—no matter how precise—is only as good asits guidance system. Simply put, it will hitwhat it’s directed to hit, which is why formost of his career, Wong has focused onthe development of better imaging tech-nologies that show where the beam isgoing.

The National Proton Center has mag-netic resonance, or MR, and CT imaging,as well as a new type of CT scan calleddual energy CT that provides detailed information on the specific makeup of atumor. This advanced and unmatchedimaging makes our proton therapy themost precise of any available today.

His latest invention, the CT Couch,brings new technology to photon andproton therapy by putting the imageguidance directly on the therapy ma-chines. Typically in radiation therapy, pa-tients must move between a simulatorand the treatment room. The simulator isa dress rehearsal of sorts that uses CT im-aging so that the physicists and the treat-ment team can visualize where tumorsare located in relation to the rest of thebody, particularly vital organs. Complexcalculations are made based on these imaging data, and the treatment plan isset in place. Until now, treatment plan-ning and treatment delivery could not bedone in the same room and usually not onthe same day.

John Wong’s Inventions1997: Active Breathing Coordinator, an interactive and noninvasive device, coordi-nates breathing with radiation treatment,locking a breath in place for a short, comfortable period to prevent movement-related radiation damage to vital organs,such as the heart or lungs.

2000: Co-inventor of cone beam computedtomography, which uses a cone of divergentX-rays and captures CT images to deliverclear images of bone, soft tissue and tumorto guide radiation delivery.

2001: The Small Animal Radiation Re-search Platform (SARRP) is a miniaturizedversion of the human machine and made itpossible, for the first time, to study humantherapies in animal models.

2013: The Raven quality assurance device connects to machines and quickly performsa series of measurements to ensure machines are functioning correctly.

2018: CT Couch integrates image guidancewith treatment delivery.

INNOVATION

“Conventional photon radiation therapy and proton therapy cure tumors at the same rate.The side effects theycan cause are similar,but with proton, lessdose goes to normalcells. That’s the benefit.”

WONG




When Jeanie, a housepainter, began havingtrouble pouring paints without spillingthem, the active 65-year-old chalked thecoordination problem up to age. Still, shecouldn’t understand why she had no prob-lem riding the waves on her boogie boardbut struggled to paint in a straight line orback her car out of a driveway. WorriedJeanie may have had a stroke, her sister encouraged her to see a doctor, and thenews was shocking. The cause of her symp-toms was three tumors in her brain that hadspread there from an advanced endometrialcancer Jeanie never knew she had.

Jeanie knew her diagnosis was unusualand dire, so the Kent Narrows, Maryland,resident opted to go to the Johns Hopkins

Kimmel Cancer Center. There, she under-went a hysterectomy to treat the endome-trial cancer. Radiation oncologist and braintumor expert Lawrence Kleinberg andneurosurgeon Chetan Bettegowda treatedthe spreading cancer in her brain. Whenfriends asked Jeanie if she planned to geta second opinion, she responded, “Afteryou’ve gotten your first opinion at JohnsHopkins, you don’t need a second opinion,”noting that she had a team of more than adozen experts collaborating on her care.

Kleinberg offered optimism when mostsaw her advancing cancer as hopeless. “Myfriends thought I was a goner, but Dr. Kleinberg always believed I had achance, and that meant so much to me,”says Jeanie.

Despite what seemed a bleak diagnosis,four years later Jeanie's cancer is now un-detectable. “I’m a bit of a miracle,” saysJeanie, who just celebrated her 69th birth-day. After the combination of chemother-apy, radiation therapy and surgery used totreat the advanced cancer, she wentthrough physical therapy for balance andcoordination issues caused by the brain tu-mors but says, “My treatment at JohnsHopkins was a breeze.”

Today, Jeanie is back to work and playingdrums with her band the Surf Jaguars.

CARE

Beating Brain Tumors

Jeanie (right) andpartner Jenny

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

cells surrounding the tumor from injury,”Kleinberg explains.

Comparing proton treatment to pho-ton therapies will be one area of research inthe Johns Hopkins National Proton Center.

The studies will be very different forthe adult patients Kleinberg treats than pediatric patients. “We know for certain thatthere are toxicities for pediatric patientswhose brains are still developing, but wedon’t know yet the extent of these toxicitiesin adult patients whose brains are alreadyformed. We will only learn this by doing research studies that compare proton therapy to other types of radiation treat-ment,” says Kleinberg.

For example, Kleinberg says, stereotactive ablative radiation or robotic ra-diation treatment with the Cyberknife, alsoprotect normal tissue. Research will showthe situations where proton therapy will pro-vide greater protection.

As protons travel through the body, most of the energy is reserved and released where the protons stop in the tumor.Photons, on the other hand, release energy along the entirepath they travel. This fundamental difference is what makesproton therapy preferential for certain tumors in the spinal cordand the brain. If vital organs or structures are along the paththe radiation travels, protons cause less damage to them. And there is no exit dose.

THE SIDNEY KIMMEL COMPREHENSIVE CANCER CENTER at JOHNS HOPKINS 19THE SIDNEY KIMMEL COMPREHENSIVE CANCER CENTER at JOHNS HOPKINS 19

Brain TumorsRadiation oncologist Lawrence Kleinbergunderstands the gravity of the cancer hespecializes in treating. The brain tumor expertknows there is not only vital functional consequences of treatment, including loss ofvision or use of arms or legs, but there is also a certain sanctity when it comes tothe brain. It is what makes us truly human,the keeper of our personality, thoughts andmemories. The world’s greatest supercom-puter makes the connections for essentiallyevery bodily process and function. When cancer and benign tumors infiltrate the brain,the consequences of treatment can often beas dire as the diagnosis.

“The type of damage that can becaused by radiation therapy depends onwhere in brain the tumor is located,” saysKleinberg. “It could affect almost any function—strength of an arm or leg, memory function,or even vision. Almost anything the braincontrols could be affected.”

As a result, Kleinberg is excited aboutthe opportunities to explore the great promiseof proton therapy for protecting the brainfrom these side effects.

The patients most likely to benefit, hesays, are those with brain tumors classifiedas low grade because they are slow growing,limited to a specific area of the brain, highlytreatable and often curable. These charac-teristics make them good candidates fortreatment with radiation, including protontherapy. These characteristics also distin-guish low-grade tumors from their highlymalignant and aggressive counterpart thatreach throughout the brain. Whether the pre-cision of the proton beam will benefit pa-tients with these types of brain tumors ismore uncertain and will require extensive re-search studies.

“The problem with highly malignanttumors is that what we are treating on purpose is mixed in with the normal brain,”says Kleinberg.

Low-grade tumors, such as menin-gioma (a benign tumor that forms on mem-branes that cover the brain and spinal cordjust inside the skull) and pilocytic astrocy-toma (a slow-growing type of glioma braintumor that originates from star-shaped cellscalled astrocytes) are more confined to aspecific area of the brain.

“Proton therapy will probably not beany better at controlling the tumor, but it maydo better job of protecting normal brain

“We have expertise in all of these options, and this is important because proton may be better in some situations, andin other instances, we may want to give bigbursts of radiation over a shorter period oftime, and in that case, other types of treat-ment may protect the brain better. It’s veryindividualized,” says Kleinberg.

Like proton therapy, some of ourother radiation treatment devices also havetumor tracking to make sure the radiationbeam stays fixed to the tumor, even if thepatient moves. This is even more vital forbrain tumors, Kleinberg explains, where tox-icities to normal brain can have life-altering consequences. Comparing thetumor tracking in proton verses other typesof radiation treatment, such as Cyberknife,is another focus of research in the protontherapy center.

The ability of the proton beam to stopat the tumor makes it the preferable option for patients with tumors that sit onor close to the spine or near other criticalstructures that need to be shielded from radiation, such as the optic nerve. Kleinbergsays proton therapy may also be thebest option to preserve fertility in women ofchildbearing age who have tumors near thepituitary gland. Whether proton therapy isthe best option will be an individualized de-cision, depending upon the shape and typeof tumor.

Its toxicity-limiting precision also pro-vides flexibility to increase doses. With othertypes of radiation treatment, doctors may de-crease the radiation dose to the tumor to pro-tect a vital structure nearby. “Proton therapyin some situations will allow us to give a bettertherapeutic dose without worrying aboutdamage to nearby structures, and that couldimprove outcome for some patients,” he says.

Kleinberg would also like to studyproton therapy’s ability to instigate thebody’s own natural defenses—the immunesystem—to attack brain tumors.

Having another tool to consider in treat-ing his patients is a good thing, but he says pa-tients come to the Kimmel Cancer Centerbecause of its reputation for excellence.

“Our patients aren’t just looking for thenext new technology. They are much moreengaged with our expertise and knowledge,as are the physicians who refer them to us.That is key,” says Kleinberg. “Patients oftencome a long way and pass a lot of centersto get to us. They do this because we haveearned that trust.”

RADIATION LEVELS

LESS MORE

ENTRANCEDOSE

BRAIN IS NOT EXPOSED TO RADIATION

Protontherapy

Photontherapy

ENTRANCEDOSE

TUMOR TARGET

TUMOR TARGET


Brian’s days were busy as he and his wifeenjoyed their active 2-year-old son. Despite a family history of prostate cancer, when the 47-year-old began feel-ing “a little off,” he didn’t initially thinkmuch of it. As his symptoms worsened,however, Brian decided to make an appointment with a urologist.

The urologist performed a prostate examand a prostate-specific antigen (PSA), ablood test that screens for prostate can-cer. The results of both tests pointed tocancer. The exam revealed an enlargedprostate, and his PSA test results werehigh. A friend recommended he go toJohns Hopkins to have it checked out.

“He said Johns Hopkins was excellent.He sort of joked with me at first saying, ‘Iwon’t be offended if you don’t go, but Ihighly recommend it. Scratch that, hesaid, I will be offended if you don’t go,’”recalls Brian. He took the advice, and tothis day, he remains grateful to his friendfor the recommendation.

His appointment with the Prostate CancerMultidisciplinary Clinic involved all ofthe specialists involved in treatingprostate cancer, including radiation on-cologist Phuoc Tran.

By the time Brian’s cancer was diagnosedin 2016, it had already spread, a distinction

known as a metastatic cancer that oftenlimits the kind of treatments a patient iseligible to receive. It also often representsa dividing line between a curable cancerand one that is not curable. However, Tranis beginning to shift that paradigmthrough a new Cancer Metastasis and Invasion Program he leads with KimmelCancer Center colleagues, cell biologistAndrew Ewald and Bloomberg Distin-guished Professor Ashani Weeraratna.

Their research shows that just as thereare varying stages and grades of cancer,there are also varying degrees of metasta-sis. A cancer that has just begun to spreadfrom the primary tumor to a few sites isvery different from a cancer that hasspread to many distant sites throughoutthe body, yet treatment is often similar,Tran explains. Popular opinion was thatonce a cancer had spread, there was nogoing back. Attempts to cure the cancerwere obviated for palliative treatmentsthat knocked the cancer back a bit andameliorated pain and other side effectsassociated with the spread of the cancer.

Tran and colleagues, including prostatecancer researcher Kenneth Pienta, how-ever, were starting to see evidence thatthere was connectivity between primarytumors and cancer cells that broke awayand formed new tumors elsewhere in thebody. They believed that selectively treat-ing these tumors with radiation and othertreatments had the potential to make cancers once thought incurable, curable.

This was the approach taken with Brian.

Tran uses the analogy of the first Ameri-can colonists. Although, they set up com-munities in distant locations, they oftenrelied upon and received support, guidance and instruction from GreatBritain, says Tran. Similarly, he believes—and research is beginning to bear thisout—that spreading cancers remain molecularly connected to the primarytumor site, where the cancer originated.

“Most experts forget about the primaryprostate tumor once a cancer has spread,”says Tran. “We’ve learned from data generated by the Johns Hopkins Rapid

“How proton therapy interacts withother therapies we already give, including immunotherapy, representsa whole untapped area of research.Combining proton therapy with other treatments is a completelynovel and promising strategy tochange proton therapy into a systemic treatment against more advanced, spreading cancers.”—Phuoc Tran, M.D., Ph.D.

Curing Cancers OnceThought Incurable


Autopsy Program that some metastaticcells go back to the prostate and travel allover, communicating with other cancercells and colonizing. Information is exchanged, and it strengthens the canceras a whole,” he says.

This connectivity and how the primarytumor communicates with colonizingmetastatic tumors are not yet fully under-stood. Although cancer metastasis is theleading cause of cancer death—account-ing for 90%—little research is aimed atfiguring out how to thwart it. Decipheringhow cancer spreads and how to interferewith the process is the mission of theCancer Invasion and Metastasis Program.

Cancer cells are the ultimate survivalists,exploiting all the tools of normal cellularand molecular biology to their advantage.There are some data that show that pri-mary tumors send out signals to lay thegroundwork for the future spread of thecancer. Later, cells go to predeterminedlocations and form new tumors. Other tu-mors remain dormant, sometimes fordecades, and then begin growing again.

“Communication is cut off, and the canceris barely surviving, but then communica-tion is restored,” Tran hypothesizes. “Thecancer may just be sitting there, not activelydividing, but then some event allows it totake off again. That’s what we need to stop.”

Tran believes cutting off the metastatic orspreading cancer cells from the primarytumor makes it more difficult for a cancerto survive. Some prostate clinical trialsare beginning to prove his hypothesis tobe true, showing that treating the primarytumor extends life. Still, many times thecancer often comes back, he says.

Tran’s vision is to take the battle to thenext step, treating both the primarytumor and metastatic sites.

This is the plan Tran, Pienta and surgeonMohamad Allaf developed for Brian,combining chemotherapy, a testosterone-blocking drug, surgery and radiation toget at the primary tumor and the spread-ing cancer cells.

Typically, surgery is not an option forprostate cancer that has already spread.Instead, doctors usually opt to cut off thetestosterone feeding the cancer, a treat-ment that can quiet the cancer down butalso have unfavorable side effects for patients, and it does not cure the cancer.

Tran says as they shift the treatment paradigm for metastatic cancers, theyneed safe and precise ways to get atspreading tumors, and he believes protontherapy could be the way. Treatmentssuch as immunotherapies that engage andimprove the ability of the immune systemto attack cancer are having success againstmetastatic cancers and may be part ofcombined treatments. “We think that protons are less immunosuppressive, sowe want to study how they interact withimmunotherapy,” says Tran.

He and Marikki Laiho, director of mo-lecular radiation sciences, have alreadybegun preparing for these kinds of protontherapy laboratory studies.

“We don’t really know a lot about pro-tons. This is our mandate. How protontherapy interacts with other therapies wealready give, including immunotherapy,represents a whole untapped area of re-search,” says Tran. “Combining protontherapy with other treatments is a completely novel and promising strategyto change proton therapy into a systemic

treatment against more advanced,spreading cancers.”

It is called the abscopal effect, Tran ex-plains. The thought behind it is thattreating the primary tumor and somemetastatic lesions can cause even untreated tumors to shrink. It goes backto Tran’s concept that the primary andspreading cancer cells are interconnected,and damaging one link in this chain isenough to weaken the entire cancer.

“The sum is greater than the individualparts,” says Tran. “Cut off the metastaticsites from the primary tumor, and it becomes more difficult for the cancer to survive.”

The treatment appears to be working forBrian, who four years later remains can-cer-free, with no signs of recurrence and aPSA of zero. He does his part to keep thecancer in check, keeping active, eating welland keeping a positive outlook.

“One of the smartest things I did was cometo the Johns Hopkins Kimmel CancerCenter,” says Brian, who got a second opin-ion at Tran’s encouragement. Troisi wentto another major comprehensive cancercenter and was advised to stick with Tran’splan. The doctor he saw noted that noother place was offering these kinds oftreatments for advanced prostate cancer.

“The most important advice I give toother people is to make sure to talk to thebest,” says Brian. “Find the people whocare about the issue you have and are onthe cutting edge. I met people around theworld when I was receiving radiationtherapy at the Kimmel Cancer Center.They told me that everyone around theworld knows Johns Hopkins.”

Tran says many patients he sees for thefirst time come believing there is nothingthat can be done for them. In their mostdifficult moment, Tran’s innovative newtreatment approach gives hope.

“My life is great,” says Brian. “I have twokids now, and my wife and I are enjoyingevery moment.”

Tran believes cuttingoff the metastatic orspreading cancer cellsfrom the primary tumormakes it more difficultfor a cancer to survive.Some prostate clinicaltrials are beginning toprove his hypothesis tobe tre, showing thattreating the primarytumor extends life.


In 2018, a cancerous tumor David had removed from his neck a decade earlier returned.

David’s cancer was classified as HPV-pos-itive, meaning it was caused by the humanpapillomavirus. Kimmel Cancer Centerresearchers identified the virus as thedriver of certain head and neck cancers in2007. Their findings marked a distinctsubtype of head and neck cancer and onethat portended better responses to treat-ment and very high cure rates.

As an engineer, David looked at things pragmatically and analytically, and he didhis research. He consulted with his doctors in Hong Kong, where he’d livedsince 1995 and had his first surgery. Theytold him HPV-positive head and neck cancer was uncommon in Hong Kong. Attheir suggestion, he began consideringtreatment back in the U.S., where he often traveled for business. He contacted experts at the National Cancer Institute(NCI) and at several NCI-designated comprehensive cancer centers.

He began receiving a standard regimen ofchemotherapy in Hong Kong as he explored radiation therapy options, includ-ing proton therapy. David’s oncologist toldhim he had accepted a position at JohnsHopkins and introduced David to KimmelCancer Center radiation oncologist andhead and neck cancer expert Harry Quon.

David’s cancer was at the base of histongue and a saliva-producing gland calledthe parotid.

“Every person I talked to prepared me forpain and suffering,” says David. “Dr. Quonwas different, and that sold me.”

While most cancer experts David consulted considered severe side effects agiven, Quon took a different view. “Wedon’t want you to be in pain. We want youto eat,” Quon told David. His goal was tominimize or eliminate side effects, andDavid said that made the Kimmel CancerCenter’s approach unique.

At the heart of what sets Quon’s approachfrom others is a desire to do better for patients, and this resulted in a programcalled Oncospace he developed withphysicist Todd McNutt. Head and neckcancers are considered among the mostdifficult to treat because they are in closeproximity to so many other organs andglands. Damage to the voice box, tongue,throat and salivary glands can make it painful for patients to eat and cause other quality-of-life-altering andeven life-threatening consequences.

McNutt and Quon developed a complex,computerized data mining system thatscrutinizes and analyzes data from priorpatients who received radiation treatmentto improve the treatment of new patients.It evaluates the therapies that worked bestfor a particular cancer and learns fromthose that resulted in less-than-favorableoutcomes to generate an optimal treatment plan. Quon used Oncospace todevelop a plan that protected David’sparotid gland from permanent damage.

David says he is grateful to Quon andnurse Marsha Freudigman for focusingon the person and not the cancer. Davidcontinued to work and remained activethroughout his treatment, exercising andusing yoga, reiki and acupuncture to support healing. “After six weeks of radiation therapy, I was eating just likeanyone else,” says David. Even better,David’s last scans show no signs of cancer.

INNOVATION

Better Treatment for Head and Neck Cancers

Patient David


Oncospace scrutinizesand analyzes data fromprior patients who received radiation treatment to improve the treatment of new patients.

Harry Quon, M.D.


Just as the trajectory of the beam is onlyas good as the guidance system, theimage guidance is only as good as thequality of the images it receives. Imagingresolution has been a challenge that oftenleads to a larger field of radiation treat-ment to ensure that cancer cells aren’tmissed.

“Imaging is critical to the process. Thebetter you can see the target, the moreprecisely you can treat with radiation,”says Wong. “If I don’t know where thetumor is, it doesn’t matter how great theequipment is.” He says proton therapyhas been delivered for many years with-out absolutely knowing for sure wherethe beam is hitting.

The CT Couch addresses this problem,introducing—for the first time—practicalin-room imaging. Some refer to it as on-board imaging, but Wong prefers CTCouch because of an essential compo-nent—the couch is part of the therapymachine, but it is not on the therapy ma-chine so it does not disturb or interferewith any of the treatment machinery.The image quality is comparable to diag-nostic-quality CT and far superior tocone beam CT—one of Wong’s earlier in-ventions—and other existing imagingtechnologies.

The proton therapy CT Couch will inte-grate radiation simulation with radiationtreatment, and because Wong is the inventor, his patented technology will beunique to the Kimmel Cancer Center’sradiation oncology clinics, including theNational Proton Center.

The idea to integrate imaging with therapy came to him when he observedcolleague Viswanathan’s novel 3D image-guided brachytherapy. One part involvesadvanced MRI guidance, and the otheruses mobile CT to check the placement ofthe implant every day to confirm thelocation of the radioactive seeds that treatcervical, uterine and vaginal cancers.

“It made me realize you could do CT im-aging with a small footprint,” he says. Thissmall footprint makes it possible to bringimaging into the treatment room withoutinterfering with the treatment equipment.

“This is precision therapy in practice,”says DeWeese. “Patients’ tumors are intheir bodies in a specific orientation, andthis differs patient by patient. One sizedoesn’t fit all,” he explains. “We have totarget each patient’s cancer differently,and we do this based on a sophisticatedset of scans before patients are treated.Those images are fused together, sort oflike virtual reality, so we know preciselywhere in the body the tumor is in relationship to the normal cells around it.”

DeWeese says a CT scan of a patient isdone to see where cancer is on the day oftreatment relative to where it was deter-mined to be in treatment planning. All ofthe images are merged to precisely aimthe beam within an incredible one-tenthof 1 millimeter accuracy.

The CT Couch will be integrated intoboth photon and proton therapy, helpingensure the treatment beam goeswhere it is intended, and perhaps more importantly, avoiding critical organs andstructures that need to be protected fromradiation treatment.

Comparative PlanningTo use proton or not to use proton is thequestion that few centers can solve.

“We own all of our machines, so we arenot driven by profit to select one machineover others. Patient care—whatever is thebest option for the patient—will guidethis decision-making,” says Viswanathan.

The Kimmel Cancer Center’s excellencein all areas of radiation therapy makes itpossible to offer comparative planning.This means the ability to determinewhich one of its many radiation treat-ment tools—proton, photon, CT- andMRI-guided brachytherapy, stereotacticablative radiation, Cyberknife—is thebest option for each patient.

“The kind of radiation our experts per-form is already very focused in conformingto the tumors. Some centers have beenso proton focused they are missing thebenefits of other types of radiation,” saysViswanathan. “Proton therapy, for exam-ple, cannot substitute for stereotacticablative radiotherapy, so the benefit of anexpert team who can make the importantcomparisons and correctly determine,patient by patient, which form of radia-tion therapy is the optimal choice cannotbe overstated.”

Stereotactic ablative radiotherapy involvesmany weaker beams that come from a variety of directions and converge atthe tumor to deliver a more precise,higher-dose beam to the cancer.

This kind of comparative planning is another unique service of the Johns HopkinsNational Proton Center. For each patient,it involves analysis of imaging and treat-ment plans for each machine to deter-mine which type of radiation therapy isthe best approach. Sometimes it may bea combination.

Every type of radiation therapy has itsplace, but most centers lack the capabilityto use data and science to make thosejudgments. “It’s not always obvious,” says

“We own all of our machines, sowe are not driven by profit to select one machine overothers. Patientcare—whatever isthe best option for the patient—will guide this decision-making.”



DeWeese, “so this is another area whereexpertise is vitally important. All plansare not created equally.”

“There are some cancers, such as those inthe brain or near vital organs, that shouldget proton therapy, but there are othercancers that would respond better to photon therapy,” explains Viswanathan.“Some patients might benefit from a com-bination of both. We may want to treat themain tumor with photons and metastaticsites or lymph nodes with protons.”

Working with our radiation oncologists,our medical physicists use supercomput-ers to iterate the plans hundreds of timesto arrive at the most ideal way to deliverradiation to each patient. The selectedplan is reviewed, modifications are madeand it is tested with a virtual avatar of thepatient to be sure it has the outcomes an-ticipated. The end product is precisionradiation therapy that has been detailedand confirmed at many levels and specific to the needs of each patient.

Oncospace and ProtonFurther informing these decisions is aKimmel Cancer Center-built data miningsystem called Oncospace.

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

Ten years in the making, Oncospace waspiloted in head and neck cancers, whichare among the most difficult cancers forradiation physicists and oncologists toplan for, says radiation physicist ToddMcNutt, who built the technology. It often requires many revisions to designa treatment that hits the cancer with radiation but does not do damage to vitalorgans and glands, such as the voice boxand salivary glands, he says.

INNOVATIONA technology called Oncospace, developed by physicist Todd McNutt,Ph.D., compares outcomes to determine when and in which patientsproton therapy is the best option.



Howard Hopkins PartnershipThe opening of the Johns Hopkins NationalProton Center will also mark the start of acollaborative medical physics program withHoward University.

Theodore DeWeese and John Wongcollaborated with Quinton Williams, chair ofthe physics and astronomy department, andPrabhakar Misra, professor of physics, atHoward University, a historically black university in Washington, D.C., to get the program up and running.

“Howard University has a top notch under-graduate program in physics and engineeringwith outstanding students,” says DeWeese.“These are exactly the kinds of students who will excel in our joint program and become great contributors to the field.”

Wong and other Kimmel Cancer Centerphysicists will be among the faculty of thenew program. DeWeese approached WayneFrederick, president of Howard Universitywith the idea when he noticed there werevery few African Americans among the 4,000members of the professional society formedical physicists.

Unity Health CareA collaboration between Unity Health Care and Johns HopkinsSibley Memorial Hospital brings a cancer clinic to underservedcommunities in Washington, D.C. The specialty services offeredthrough this collaboration will provide much-needed cancer careto underserved patients in Wards 7 and 8, who have some of thehighest cancer rates in the country, and other areas throughoutthe District of Columbia.

The Parkside Health Center will serve as home base for the clinic. A nurse navigator will help patients overcome barriers to care andfacilitate timely access to treatment at the Johns Hopkins Kimmel Cancer Center and Johns Hopkins National Proton Center.

CARE

Kimmel in the Community


With such vulnerable anatomy close to the tumor, radiation can impact thefunction of untreated glands as much asthe treated glands, explains McNutt. Instead of looking at each gland as an in-dependent organ, he says Oncospacehelps them analyze it all together. It’scalled inter-organ dependency, and heand collaborators, like head and neckcancer expert Harry Quon, are the first touse such complex computer analysis to un-derstand it and improve care for patients.

“All of these glands work together to pro-duce saliva. If I give a high dose of radia-tion to one gland, we have to know howmuch function we have to preserve in allof these other glands to keep salivary production at a comfortable level,” saysMcNutt. “If I overdose this ductal region,I may render some portion of the rest ofthe gland useless.” Although the glandmay still function, it blocks the flow ofsaliva, making it difficult to eat, causingpain and often leading to oral infections.

Oncospace quantifies, measures and an-alyzes all of the variations in treatmentsand toxicities in patients already treatedto inform the care of new patients. Everypatient treated adds to the data, so it isever improving as new data—and moretypes of data, such as physician notes andimaging—are included.

“There is knowledge in the variations intoxicities and response that occur frompatient to patient, and this type of analysisis only possible with the analytic capabil-ities of Oncospace,” says Quon.

It’s a tool that no other cancer center inthe world has, and Quon says it has beeninstrumental in improving patient care.He credits it with attracting people to theKimmel Cancer Center’s head and neckcancer practice.

McNutt’s system provides the guidancethat allows Quon and other clinicians tomaximize healing and minimize harm. Itscours all of the data on head and neckcancer patients treated in the KimmelCancer Center; charts radiation dose distributions, toxicity and other data in

vividly colored computerized maps andgraphs; and reveals the optimal plan. Atthe same time, it takes into account andconnects all of the variables—age, underly-ing health conditions and other treatmentspatients are receiving—and figures outhow all of these variables relate and influ-ence toxicities and response to treatment.

They are even exploring the physiologi-cal features of glands and the potentialrole they play. Information like texture,fat content, fibrous connective tissuearound glands and overall health of sali-vary glands are entered into Oncospaceto help guide individualized treatmentplans for patients.

Oncospace uses a type of artificial intel-ligence known as machine learning tolook back at the patterns of dose withinthe anatomy and how these doses relatedto patient outcomes. In head and neckcancer, McNutt and Quon know there arestem cells throughout the glands that ini-tiate the healing that keeps the glandshealthy. By querying Oncospace, theyfound that varying the dose of radiationmay be the key to protecting these stemcells and ensuring that salivary functionreturns after radiation.

“This is one of the things we are most excited about studying in the proton cen-ter,” says Quon. “Now when we have togive radiation close to areas that we thinkcontain these repair stem cells, we have thecapability to stop the proton beam on adime. That makes it possible for us to keepradiation at a low dose in these criticalstem cell regions. It gives us some new options.”

Proton therapy, he says, offers the abilityto improve patterns of dose because it isso targeted. Oncospace also comparesphoton and proton treatment outcomesto determine when and in which patientsproton is preferable and when photonmay be the better option. It is one moretool that helps our experts know the bestway to use proton therapy.

No one else is doing this because no one elsehas the technology to quantify and measure

the myriad of contributing factors to makethese incredibly complex calculations.

McNutt is now beginning to apply thesame analytical tools to decrease swal-lowing problems, potentially life-threat-ening scarring of the larynx and the lessserious but nonetheless troubling impacton taste for head and neck cancer patients getting radiation. They are alsoexploring how to use Oncospace to predict risk of cancer recurrence, and which patients will likely benefitfrom treatment with immunotherapy,and identify patients who would mostbenefit from receiving radiation therapyafter surgery. Oncospace is also being ex-panded to mine other cancers, includingesophageal, lung, pancreatic, prostateand pediatric cancers, with the goal ofusing it to inform the treatment of everycancer type. Ultimately, he would like tomake the technology available to expertsthroughout the U.S. and the world.

Experts from Japan, a country with along history of treating cancer with proton therapy, are coming to the Kimmel Cancer Center to collaboratewith McNutt and discuss including theirdata in the system.

“The truth is no one can keep treatingwith protons without the evidence andguidance Oncospace provides,” Quonsays. He hopes other proton centers willwant to collaborate.

“This kind of inventory opens up a lot ofopportunities,” says Quon. “The data’svalue is not just defined by what you wantto do now but also by the possibilities ofwhat we can do in the future.”

“Now when we have to give radiation close to areas that we thinkcontain these repairstem cells, we have thecapability to stop theproton beam on a dime.”



Like adult patients, pediatric patients receive radiation therapy as treatment fora variety of cancers. Brain tumors are the most common solid tumor in childrenand the cancer where most experts agree proton has the edge because of itsability to so precisely spare surroundingnormal cells.

It is clear that every patient does not needproton therapy. “It’s a necessary tool tohave to use at certain times, but not everytime,” says DeWeese. “We look at each pa-tient—pediatric and adult—individually tobring the best technology and treatmentplan we have to bear against their cancer.We look at anatomy of where the tumor is

and what is the best approach to kill thecancer and preserve everything else.”

In fact, how to lessen the adverse effectsof radiation has long been an area of research among the Kimmel Cancer Center’s pediatric radiation oncologists.

Although it is generally accepted thatproton therapy provides benefit overother types of radiation therapy for pediatric patients, research studies arelacking, and our experts understand better than most the important role oflaboratory and clinical science in settingthe standard of pediatric cancer care.We’ve been leaders for more than a half-century.

When the National Cancer Institute established four study groups to investigatecommon childhood cancers in the late1970s, Johns Hopkins radiation oncologistMoody Wharam was the only expert appointed to two of the groups. From 1980to 1990, he served as director of the radia-tion oncology committee of the PediatricOncology Group, now known as the Chil-dren’s Oncology Group, the world’s largestorganization devoted exclusively to child-hood and adolescent cancer research.Wharam and Kimmel Cancer Center col-laborators were active participants in all ofthe pivotal pediatric cancer research of thetime—research that led to dramatic increases in pediatric cancer survival rates.

COLLABORATIONPatients have access to the combinedexpertise of Children’s Nationaland the Johns Hopkins Kimmel Cancer Center.

PediatricsA collaboration with Children’s National

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


“The way we manage radiation therapy inchildren today is based on what he didthrough all those years of tireless work.That’s why we do research,” says DeWeese.

The cruel irony that the radiation treat-ments given to save the lives of young patients also has the potential to causeharm continues to trouble radiation oncologists. Radiation to growing bonesand organs can impede normal develop-ment, and radiation to the brain, a common site of pediatric cancers, toooften results in impairments to learningand other cognitive brain functions.

In this long history of improving care forpediatric cancer patients, proton therapyis viewed as another major advance inmanaging late effects of radiation therapy.Matthew Ladra, director of pediatric radiation oncology, is eager to begin proton therapy studies. Ladra was thefirst radiation oncologist to earn a protontherapy-specific fellowship, which hecompleted at Massachusetts GeneralHospital. This training led to a director-ship of the pediatric service at the Provision Center for Proton Therapy inKnoxville, Tennessee.

Jen Holt, who also worked at the Provision Center, joined Ladra as nursemanager for the pediatric radiation oncology program.

“When children get exposed to radiationat a young age, they are at much higherrisk of issues down the road when theyare long-term survivors,” says Ladra. He is among a select number of radiationoncologists whose practice and researchfocus solely on pediatric cancers. “Ourgoal is to radiate what’s supposed to beradiated and leave everything else alone.Proton therapy helps us do that.”

The ability to better steer protons to the cancer and stop the beam means developing brains, the heart, lungs andgrowing bones can be better protected.

Ladra says he has seen the benefits. Herecalls brain tumor patients he treatedwith proton therapy who have none ofthe telltale signs of a brain tumor battle.“They have no cognitive issues. They aregrowing normally. It’s very rewarding,and the technology we have at JohnsHopkins is even better, and that meansthere are still advances that can be made,”says Ladra.

Still, he knows that there is a differencebetween anecdotal reports of benefitsand scientific evidence. The latter is a keyelement that has been missing from theconversation.

Novel research, including a map of thebrain that relates dose of radiation to im-pact on specific areas of the brain, show-ing the maximum dose of radiation eacharea of a young brain can tolerate withoutcausing functional deficits, is providinginformation that other centers don’thave. It is revealing areas that will requiresmaller doses of radiation but also othersthat could safely tolerate larger doses.

The opportunity to study the benefits ofproton therapy is what attracted him tothe Kimmel Cancer Center. The JohnsHopkins National Proton Center is onlyone of two in the country that has a dedicated pediatric facility and a protonresearch program.

The ability to bettersteer protons tothe cancer andstop the beammeans developingbrains, the heart,lungs and growingbones can be better protected.Reducing an unnecessary dose is a good thing.

Nanoparticles andOrganoids Pediatric radiation oncologist MatthewLadra is experimenting with protons,nanoparticles and organoids to deliver prom-ising new therapies to pediatric patients.

One study uses nanoparticles—ultra-tinystructures that can transport a cargo ofdrugs and other cancer-fighting treatmentsto tumors—to reset cells’ natural cancer-fighting DNA. Ladra says that many pediatriccancers are missing a key tumor suppress-ing gene, called P53, and the nanoparticlestransport the gene to cancer cells to put it back into action.

“We use proton therapy to stun the tumorand open it up so we can infuse radiolabeledp53 genes,” he says. The gene is alreadypresent in normal cells, so it only goes towork in tumor cells. The radiolabel allows thescientists to see and track the gene insidecancer cells to confirm that if it turns on andhelps shrink the tumor.

Ladra also plans to collaborate with drugdiscovery experts and other scientists tostudy drug/proton combinations. In pediatricbrain tumor research, he is excited about anew model of discovery being used by radiation molecular scientist Sonia Franco.Tiny, organized spheres of human neural andnerve cells about the size of a fly’s eye,called organoids or minibrains, are providingan innovative way to research treatments ofpediatric brain cancers. Franco is using themto replicate how pediatric brain cancers naturally grow and spread, and to studymore closely how these cancers respond toradiation and drug treatment. In a precisionmedicine approach, a minibrain could be created as a stand-in for a patient by implanting it with cells from the patient’sbrain cancer.


“This is a truly visionary approach. Research is the only way to get at concrete evidence of the advantage ofusing protons to treat children and toshow us how we can improve the care ofkids moving forward,” says Holt.

The dedicated pediatric oncology servicehas its own team of experts—radiationoncologists and technicians, pediatricnurses, including a nurse practitionerand nurse navigator, a child life specialist,a nutritionist, survivorship and familycounselors, and a pediatric anesthesiolo-gist, as very young patients often requiresome sedation during treatment.

“The proton therapy technology is muchbetter now, and we will have the mostup-to-date proton facility, but expertiseis critical,” says DeWeese. “Like anythingelse, it has to be done well. We are learningnow that there can be issues with protontherapy when not done correctly.”

Proton therapy may also be a better op-tion for pediatric patients with sarcoma,cancers of the bone and soft connectivetissue. Sarcomas are particularly chal-lenging to treat because they often occurin the vicinity of other vital anatomy and

growing organs. With its precision, theproton beam offers the ability to get atthe cancer without harming these nearbystructures. As a result, experts believe itmay help patients avoid amputation.

Spinal tumors, cancers in the head andneck, tumors that are close to other organs—which in the small bodies of children can be many—and abdominaland pelvic tumors are also well-suited toproton therapy.

For example, a toddler with a tumor sitting close to growth plates in the pelviscan be treated with proton therapy toprotect the pelvic bones from radiationdamage that can cause the growth platesto close, resulting in growth issues andother problems later in life. In other can-cers, such as Hodgkin lymphoma, that re-quire radiation to the chest, protontherapy can protect the heart and lungs.In other cases, another type of radiationtherapy may be preferable.

“Proton therapy is an essential tool tohave at certain times, but it’s not the onlytool,” says Ladra. “We look at anatomy ofwhere the tumor is and what we need to preserve and decide on case by case if the

patient would most benefit from protontherapy.”

A teenage patient recently treated for osteosarcoma that had spread, creating agolf ball-sized tumor in the patient’s lung,benefited from stereotactic ablative radiation. Surgery was not an option because of pre-existing damage to thelung. Immunotherapy with drugs aimedat boosting the immune system to attackthe cancer was not keeping the cancer incheck, so the multispecialty team of doctors decided to use stereotactic radiosurgery to go after the tumor in herlung. The tumor disappeared, and the patient remains cancer-free.

The combined treatment of immunother-apy and stereotactic ablative radiation allowed her to avoid more toxicchemotherapy that is frequently ineffec-tive against advanced osteosarcoma. For the teenager, who was about to beginhigh school, it was also a quality of lifeissue. She didn’t want her hair to fall out,and the radiation/immunotherapy combination worked better against her cancer without altering her appearance.

Working in collaboration with experts atthe Bloomberg~Kimmel Institute forCancer Immunotherapy, our radiationoncologists uncovered evidence that cancer cells killed by radiation signal theimmune system as they die, revealingtheir identity as a cancer cell and settingcancer-killing immune cells into action.Similar studies are planned combiningimmunotherapy and proton therapy.

“In a center with so much strength inevery area of cancer research and ther-apy, we have more information to help inform our treatment decisions, and thatleads to novel, patient-centered medicineand better outcomes,” says Holt. “Thereare so many things available here—comparative planning, specialized nursingcare, multispecialty collaboration—that are not available at other places. Thefact that we’re different from most of the proton centers out there is also whatmakes us better. Our patients get it, andtheir parents get it.”

COLLABORATION“This shows how two nationally respected institutions came together in a collaborative andstrategic way to change the face of pediatric cancer.”

Kurt Newman, M.D. (left) and Theodore DeWeese, M.D.


The knowledge about the cancer beingtreated must be equivalent to the protonexpertise, Viswanathan stresses. Themultispecialty approach the KimmelCancer Center uses means each patient’scare is informed by every specialist. Ra-diation oncologists, medical oncologists,pathologists, nurses, surgeons and otherexperts work together to evaluate everycase and develop the best treatment plan.“This multidisciplinary component is soimportant because what really makesproton therapy at the Kimmel CancerCenter special is what our experts bringto it,” she says.

Unique CollaborationIt is this kind of pioneering influence thatearned the radiation oncology programdistinction as one of a select few in the na-tion with a long and proven track recordof excellence in treating pediatric cancers.

In 2013, it helped pave the way for acollaboration with Children’s National.It creates one of the largest pediatric

radiation oncology programs in the coun-try, and the increase in patient volumepromises to speed clinical discovery.

“It is another example of our strategicfocus to consistently partner with organ-izations in the region to bring high-qual-ity, accessible care to children andfamilies,” says Elizabeth Flury, Execu-tive Vice President and Chief StrategyOfficer at Children’s National. “When webase our strategic decisions aroundwhat’s best for the child, everyone wins.This collaboration is a perfect exampleof that thinking.”

DeWeese believes it is a national model.“This shows how two nationally re-spected institutions came together in acollaborative and strategic way to changethe face of pediatric cancer care in the re-gion and around the world,” he says.

Through the collaboration, patients haveaccess to the combined expertise of Chil-dren’s National and the Kimmel Cancer

CAREThe dedicated pediatric oncologysevice has its own team of experts,including pediatric anesthesiologistEugenie Heitmiller, M.D. (right).

Center’s pediatric oncology program. TheKimmel Cancer Center’s pediatric cancerprogram has consistently been ranked byU.S. News & World Report as one of the toppediatric cancer programs in the country,and Children’s National was also ranked asone of the top five children’s hospitals inthe country. The collaborations includejoint clinical trials and research initiativeswith the National Institutes of Health.

“Working together through an integratedradiation oncology service—including re-search—we are providing important newtreatment options for kids fighting can-cer who live in the national capital areaor who travel here to take advantage ofour joint expertise,” says Kurt Newman,President and Chief Executive Officer ofChildren’s National. The joining of thesetwo leading programs marks a significantachievement in children’s health, he says.

The collaboration represents the first pediatric radiation oncology program inthe national capital region. DeWeese says


Ezaylen’s “Zay Zay’s” mom, Phyllice,instinctively knew something serious waswrong when 2-year-old Zay Zay experi-enced persistent high fevers and constantear infections. Although her mother’s intuition was correct, she never imaginedthat the fevers and a protruding tummyshe chalked up to a healthy appetite were actually Wilms tumor, a type of pediatric kidney cancer. Two-year-old Zay Zay was diagnosed with stage III cancer, and the tumor was occupying a shocking 90% of his kidney.

After chemotherapy and surgery to removethe diseased kidney, his Children’s Nationaldoctors recommended radiation therapy as part of the treatment plan and referredhim to Matthew Ladra, director of pediatric radiation oncology at the Johns HopkinsKimmel Cancer Center at Sibley MemorialHospital.

“I was very concerned at first,” says Phyllice,who was aware of the side effects radiationtreatment can have on young, growing children. “My husband convinced me wehad to do it. The treatment would help makesure no cancer cells survived.”

It’s a decision Phyllice has never regretted.“Johns Hopkins is awesome,” she says. “Dr. Ladra is a great doctor. We had a goodconnection from the start, and everyone—doctors, nurses, child life teachers—stayed in constant communication with us, explaining the therapy and involving us every step of the way.”

One year later, Zay Zay’s treatments appearto be working, she says. He still has morechemotherapy ahead of him, but he haslived up to his love of superheroes and her nickname for him—little firecracker. She says, “He’s small but powerful.”

CARE

Zay Zay the Superhero


COLLABORATIONThe Johns Hopkins/Children’sNational collaborative creates oneof 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

Jean Wright, M.D.

Theodore DeWeese, M.D.

the dedicated, multispecialty team bringsthe most advanced therapy and the high-est level of safety and quality care for pediatric patients and families.

“There are cases in which radiation is the best way to enhance treatment for a young patient,” says Jeffrey Dome, Oncology Division chief at Children’s National. “This collaboration is focusedon finding the best strategies based in current research to integrate radiation therapy into a comprehensivecare regime.”

Built on Tradition So many things in cancer research havetheir roots in the Kimmel Cancer Center. It is this convergence of expertise thatmakes the Johns Hopkins National Proton Center stand out among others.Kimmel Cancer Center scientists and clinicians bring expertise to all areas ofthe cancer compendium and are amongthe undisputed leaders in cancer genet-ics, epigenetics and immunotherapy. Addto that Magnet nursing status recognitionfor quality of care, one of the first pro-grams to study late effects of cancertreatment and complete integration ofcancer services across all Kimmel CancerCenter locations, and before its doorseven open, the Johns Hopkins NationalProton Center distinguishes itself amongcancer centers and proton centers alike—in the Baltimore/Washington region andaround the country.

To ensure quality of care and access toproton therapy among all of our sites, radiation oncologist Daniel Song willlead regional chart rounds to discuss pa-tient cases across all Kimmel CancerCenter locations, including Sibley, Subur-ban, Green Spring Station, Johns Hop-kins Bayview Medical Center and JohnsHopkins Hospital. Jean Wright willoversee safety and quality across all loca-tions. Clinical nurse specialist Jen Wei-worka bridges all of the sites, overseeingintensive training for nurses to ensurethe same standard of care exists at everyKimmel Cancer Center location.

In addition to the cancer acumen of lead-ers in every field of cancer research andtreatment, the National Proton Center hasat its disposal the brain trust of all of TheJohns Hopkins University to lend theirexpertise and advance the application ofproton therapy alone and in combinationwith other cancer treatments. Thisprogress is in line with everything else ourexperts are doing to make cancer thera-pies work better for patients while alsolimiting toxicities. Targeted drug thera-pies, organ-sparing surgeries and lesstoxic proton therapy all have this goal.

Two specialized institutes will also sup-port our proton center. A new Transla-tional Convergence Institute bringsdoctors, nurses, astronomers, engineers,computer scientists, physicists, bioethi-cists, biologists, materials scientists andmathematicians together to work side byside to amass and apply their knowledge tocancer. They will solve complicated andvexing problems, build new technologiesand consider out-of-the-box, creativenew approaches that can only be foundthrough this type of directed collabora-tion.

The Bloomberg~Kimmel Institute forCancer Immunotherapy will help inte-grate proton therapy with immunother-apy, revolutionary new treatments thatactivate the immune system to attackcancers. A Drug Discovery and Develop-

ment program will advance combinedtreatments with new targeted therapies,and a first-of-its-kind Cancer Invasionand Metastasis Program, co-lead by radiation oncologist Phuoc Tran, willstudy proton therapy, among other treat-ments, to transform the management ofadvanced cancers.

“We can bring together so many thingsthat are not available at other places. Thiswealth of expertise means we have moreinformation coming, more people informing decisions and solving prob-

lems, and that leads to better outcomes for patients,” says Akila Viswanathan.“We approach cancer from all angles.There is not one single preferred solution. Sometimes it is a combinationof therapies.”

Viswanathan says one of the most impor-tant collaborations will be with the community of primary care providerswho choose us to work with them to develop the optimal treatment plans fortheir patients.

“The Johns Hopkins National Proton Cen-ter is one of the few comprehensive protoncenters in the world. Wewill be doing researchthat has never been donebefore,” says DeWeese.“It’s going to be a hugeadvance for the field.”

“We can bring together so many thingsthat are not available at other places.This wealth of expertise means we havemore information coming, more peopleinforming decisions and solving problems,and that leads to better outcomes forpatients. We approach cancer from allangles. There is not one single preferredsolution. Sometimes it is a combinationof therapies.”

New on the WebWatch our new video about the Johns HopkinsNational Proton Center.hopkinscancer.org

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