ON TARGET - The Precision of Proton Therapy Care. Collaborate. Create - Johns Hopkins Medicine
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ON TARGET
THE JOHNS HOPKINS KIMMEL CANCER CENTER
T H E N E W S M AG A Z I N E O F T H E D E PA RT M E N T O F R A D I AT I O N
O N C O LO G Y A N D M O L E C U L A R R A D I AT I O N S C I E N C E S
The Precision of
Proton Therapy
Care. Collaborate. Create.
2021-2022
ON TARGET
T H E N E W S M AG A Z I N E O F T H E
D E PA RT M E N T O F R A D I AT I O N
O N C O LO G Y A N D M O L E C U L A R
R A D I AT I O N S C I E N C E S
PROTON THERAPY
Announcing the Latest Advances in
Care as we Collaborate to Create the
Region’s Best Proton Therapy Center
Proton therapy is a rare commodity, Viswanathan, M.D., M.P.H., Director of
CARING ABOUT OUR patients is our top with less than 40 centers in the U.S. the Department of Radiation Oncology
priority. Combining advanced technol- The level of care, collaboration and and Molecular Radiation Sciences.
ogy with compassionate care is the innovation that the Johns Hopkins As a result, what truly is new in pro-
hallmark of Johns Hopkins Medicine. Proton Therapy Center brings to this ton therapy is what the Johns Hopkins
Innovations beyond standard technol- treatment is even rarer. The Proton Proton Therapy Center brings: the
ogy set us apart from a routine experi- Therapy Center is among the very few laboratory and clinical research to make
ence. These innovations are the result that will combine cancer treatment it better and to advance its use as a tool of
of the unsurpassed level of expertise in excellence across all disciplines with precision medicine. Our proton therapy
radiation oncology, molecular radiation proton therapy excellence. center is among a select few academic
sciences, physics, surgical oncology, Building upon a lengthy history and centers in the country — and the only in
medical oncology, cancer biology, engi- strong foundation of pioneering dis- the region — doing research to determine
neering, quantitative sciences and coveries in radiation therapy, this cen- in which situations this type of radiation
more that Johns Hopkins Medicine ter has the technology to deliver the treatment is the best option.
and the Johns Hopkins Kimmel Cancer most advanced and patient-centered “Proton therapy is an incredibly
Center bring to proton therapy. This care. The translational ingenuity that complex and precise tool, and there is
level of knowledge and multispecialty merges laboratory discovery with clin- still much to be done for experts to
collaboration is fundamentally what ical care thrives in the Kimmel Cancer harness it full potential,” says Christina
sets the Johns Hopkins Proton Therapy Center. It was engaged throughout the Tsien, M.D., brain tumor expert at the
Center apart from most other proton planning and construction of our pro- Johns Hopkins Proton Therapy Center.
centers across the U.S. Expertise ton center. As a result, it is one of the “We will be able to leverage our
matters because the real value of the most comprehensive in the world, one extraordinary research and clinical
proton beam is in the specialists who of the very few with dedicated proton talent in order to advance the field,”
develop it and use it. beams for research and a specialized says Viswanathan.
pediatric team. Proton therapy does not replace
Proton therapy is not new, and the other forms of radiation therapy.
science is far from settled. “Although it “We do well with all forms of radiation
has been around for a long time, it is therapy, including stereotactic and
very much in its infancy in terms of brachytherapy treatments, and that’s
research and potential,” says Akila something most other proton centers do
THE JOHNS HOPKINS KIMMEL CANCER CENTER 3 collaboration Clockwise, top left: Akila Viswanathan, M.D., M.P.H., Director of Radiation Oncology and Molecular Radiation Sciences; Matthew Ladra, M.D., M.P.H., Director of Pediatric Radiation Oncology; Christina Tsien, M.D., Proton Therapy Brain Tumor Specialist; Curtiland Deville, M.D., Proton Therapy Center Medical Director; Jean Wright, M.D., Director of Breast Cancer Program, Dept. of Radiation Oncology and Molecular Radiation Sciences; Jeffrey Meyer, M.D., gastrointestinal cancer expert; Brandi Page, M.D., head/neck cancer expert; Russell Hales, M.D., Director, Thoracic Oncology Program.
4 THE JOHNS HOPKINS KIMMEL CANCER CENTER
not offer. That’s important because not The Place for Research
every patient will need proton therapy,”
Most experts agree that the ability of
says Viswanathan. “Patient care, what-
proton therapy to spare healthy cells, The Johns Hopkins Proton
ever is the best option for the patient,
by zeroing directly on and stopping Therapy Center
will guide our decision-making.”
at the end of tumors, makes proton What Sets Us Apart
The Kimmel Cancer Center’s excel-
therapy the radiation treatment of
lence in all areas of radiation therapy Unparalleled Expertise: Since opening as
choice for pediatric patients and adult one of the first comprehensive cancer centers
makes it possible to offer comparative
patients with tumors in the brain or in the nation, Johns Hopkins Kimmel Cancer
planning. This means the ability to
on or near the spinal cord, but defini- Center experts have led cancer research,
determine which one of its many radia-
tive research studies are essential to deciphering the causes of cancer and
tion treatment tools — proton, photon,
advances. One room in the proton advancing care for the most complex cancer
CT- and MRI-guided brachytherapy,
center will be dedicated to the cellular, cases. This level of expertise continues with
stereotactic ablative radiation, our Proton Therapy Center, which will be
physics and animal studies needed to
CyberKnife or brachytherapy — is directed by the leading radiation oncology
refine and define who is best treated
the best option for each patient. and medical physics experts in the world.
with proton therapy.
Clinical Director and Proton Therapy Largest and Most Advanced: Our 80,000-
SOME CANCERS, SUCH AS Center Medical Director Curtiland square-foot facility is one of the largest and
most advanced facilities in the world, with
THOSE IN THE BRAIN OR
Deville, M.D., says it is the reason he
four treatment gantries and dedicated
came to Johns Hopkins. “I wanted to
research-specific space.
NEAR VITAL ORGANS, SHOULD be in an academic center to be at the
forefront of solving issues and questions
Imaging Couch and Respiratory Gating:
GET PROTON THERAPY.
It is the only proton center with CT imaging
about proton therapy: What are the integrated with treatment to ensure the most
best indications for proton? Where accurate and precise treatment planning and
can we increase benefit, and where can delivery of proton beam therapy. Respiratory
“The kind of radiation our experts
we reduce toxicity? Where are we not gating technology tracks the proton beam to
perform is very focused in conforming
getting such benefit and can let go? movement of the tumor and stops the beam
to the tumors,” says Viswanathan.
This is an area that is lacking, and our if the tumor moves. Our experts helped
“The benefit of an expert team that can invent and develop these technologies.
center can begin to get to the answers.”
make the important comparisons and
The Proton Therapy Center will be Pencil Beam and Other Advanced Technolo-
correctly determine, patient by patient, gies: It has the latest pencil beam delivery
solving these unknowns and leading
which form of radiation therapy is the that virtually paints tumors with cancer cell-
future progress, says Deville.
optimal choice cannot be overstated.” killing radiation while sparing surrounding
Radiation oncologist and gastroin-
Some cancers, such as those in the normal tissue.
testinal cancer expert Jeffrey Meyer,
brain or near vital organs, should get Research Center: As an academic proton
M.D., was drawn to Johns Hopkins for
proton therapy, Viswanathan explains. therapy center, research will be performed in
the same reason. Meyer completed a
“Some patients might benefit from a a dedicated gantry using specialized Johns
fellowship in proton therapy and says
combination of types of radiation or Hopkins expertise in physics and radiobiology.
that the Johns Hopkins Proton
chemoradiation. Recent data indicates Precision Medicine: Our experts take a unique,
Therapy Center is one of the few
signficantly less side effects with multidisciplinary and precision medicine
centers addressing complications approach that brings together all specialists
proton therapy for patients receiving
associated with proton therapy, such and experts to work with patients to develop
concurrent chemotherapy.”
as movement of organs and sensitivity individualized, detailed treatment plans
Working with our radiation oncolo-
to density in organs. All of these specifically suited to each patient.
gists, our medical physicists use very
questions and concerns can be Local, National and International: The Johns
fast computers to iterate the plans
mitigated with research, he says. Hopkins Proton Therapy Center brings the
hundreds of times to arrive at the most
“There are always going to be new most advanced cancer care to patients living
ideal way to deliver radiation to each
technologies. Expertise and the will- in the region while also providing care to pa-
patient. The selected plan is reviewed, tients across the U.S. and around the world.
ingness to do research to know how
modifications are made and it is tested
to use it is critical,” Meyer says. “It’s Access for All: Collaboration between the
with a virtual avatar of the patient to Johns Hopkins Kimmel Cancer Center and
a great technology we want to take
be sure it has the outcomes anticipated. Children’s National ensures advanced cancer
advantage of, but we have to be smart
The end product is precision radiation care to patients of all ages, including children
about how we use it.”
therapy that has been detailed and and young adults.
confirmed at many levels and specific
to the needs of each patient.
The Synchrotron HOW IT WORKS
A synchrotron is a type of
particle accelerator used
to accelerate protons for
Inside Our Proton
use in proton therapy. It
is 26 feet in diameter and
Therapy Center
composed of a ring of The proton is small, but it takes big
small magnets. Protons
are injected into the ring machinery to generate and move these
and begin traveling around
the ring at great speeds, subatomic particles for treatment.
about 10 million times per
second. Put another way,
the speed of the protons
is so fast, it could circle
around the earth five
times in one second. It
is advanced technology
over earlier generations
of proton therapy because
it can produce beams of
a wide range of energies Gantries
and reduces the risk of Protons travel down
unnecessary and unwanted magnetic devices into
radiation to the patient. the treatment rooms.
A 360-degree, rotating,
30-foot-diameter iron
framework, called a
gantry, controls the
speed and direction
of protons. It allows
radiation oncologists to
Pencil Beam Scanning
direct the beam at any
This new technology funnels
angle and deliver the
the protons into a narrow
Respiratory Gating proton beam with
beam—just a pencil tip’s
The slightest motion pinpoint accuracy
width—coming out of the
can cause tumors to a patient’s cancer.
proton therapy machine
hundreds of times per to move. Our proton
therapy beam tracks Our center has four of
second, scanning the tumor
directly to the tumor, these, three rotation
back and forth and up and
stopping if the tumor for adult and pediatric
down, just to the edges of
shifts with the patient’s treatment, and one
the tumor, to paint it layer by
breathing and starting fixed beam for much-
layer with the cancer-killing
up again when the needed research.
proton beam. Our advanced
technology is intensity mod- beam and tumor are
ulated, making it possible aligned.
to deliver varying degrees
of energy targeted to the
specific composition of
each area of the tumor.
On-Board Imaging
Ours will be among the first to have on-board
imaging. Plans for a CT Couch, invented by
medical physics Director John Wong in
collaboration with Hitachi, will provide a
built-in CT scanner that merges images of
the cancer taken during treatment planning
with ones taken the day of treatment to verify
that the tumor being treated has not changed
or moved. It facilitates precision treatment
within one-tenth of 1 millimeter accuracy.
6 THE JOHNS HOPKINS KIMMEL CANCER CENTER
Collaboration among Kimmel
Q&A
Cancer Center molecular radiation
scientists and the manufacturer of
our proton therapy system means our
WHAT IS PROTON THERAPY?
Proton Therapy Center will usher in
Proton therapy is an effective way of killing more advanced tumor monitoring that
cancer while minimizing harm to healthy, makes the already safe and targeted
surrounding tissue. What sets proton therapy pencil beam patient-specific and even
apart is that it literally “paints” cancerous
tumors, layer by layer, killing the cells with a
more tumor-specific. One method uses
high-energy pencil beam. Our highly trained molecular monitoring to evaluate the
team of physicians and physicists directs tumor and adapt radiation treatment
the proton beam to the desired site with to each patient. Molecular imaging
pinpoint accuracy, and treatment is con-
formed to the size and shape of the tumor.
allows doctors to differentiate cancer
The proton beam releases its energy
entering the tumor and stops at the tumor. As protons travel through the body, most of the energy
There is no exit dose, so the risk of harm to
healthy surrounding tissues is reduced. As a
Advanced Technologies is reserved and released where the protons stop in the tumor.
Photons, on the other hand, release energy along the entire
Even before the research begins, path they travel. This fundamental difference is what makes
result, proton therapy may lower treatment proton therapy preferential for certain tumors in the spinal cord
side effects and improve patient outcomes. Viswanathan is confident that the and the brain. If vital organs or structures are along the path
the radiation travels, protons cause less damage to them.
Johns Hopkins Proton Therapy Center And there is no exit dose.
WHAT CANCERS DOES PROTON is poised to deliver unprecedented
THERAPY TREAT?
care. Our 80,000-square-foot proton Photon
Because of its precision, proton therapy is
therapy center is the largest in the therapy
preferred for adult and pediatric patients
with brain and spinal tumors. In children, country and has four rooms, including
cancers can be treated without harming three with gantries — the large,
developing brains and growing bone. Since
the proton beam conforms to the tumor and
sphere-shaped structures that house
does not have an exit dose, it minimizes the equipment used to deliver proton ENTRANCE
DOSE
radiation going to normal cells, which can therapy to patients. The gantry rotates
result in the development of second cancers around the patient, delivering the
later in life. This is particularly important for
pediatric and young adult patients. Proton
proton beam at any angle necessary TUMOR TARGET
therapy may also be useful for certain to target the cancer.
patients with sarcoma, breast, prostate, Unique features, including the pencil
lung, head and neck, liver, and pancreatic beam, a tumor-tracking system that
tumors. The proton beam, with its precision
accuracy, is also favored when tumors are
allows the beam to adjust to tumor
resting near the heart or major arteries and movement, in-room imaging via a CT Proton
blood vessels. couch and the Oncospace data registry therapy
are unique to the Kimmel Cancer
IS PROTON THERAPY RIGHT FOR YOU?
At Johns Hopkins, unique multidisciplinary
Center, and make the proton therapy ENTRANCE
DOSE
clinics evaluate each patient to determine if we provide the safest and most advanced
proton therapy is the right treatment. They available.
offer patients a comprehensive consultation Our Proton Therapy Center is out-
with the entire team of experts, including TUMOR TARGET
our proton therapy experts. Our physicians
fitted with the most up-to-date pencil
and nurses work with patients to develop beam technology, which only recently BRAIN IS NOT
EXPOSED TO
an individualized, detailed treatment plan became available. The pencil beam RADIATION
specifically suited to each case. paints tumors with cancer cell-killing LESS MORE
WHY DOES EXPERTISE MATTER?
energy layer by layer, staying within the RADIATION LEVELS
Technology is only as good as the experts boundaries of cancer. The technology
who use it. The Johns Hopkins Kimmel Can- is so advanced that it is able to modu- cells from scar tissue or other ambigu-
cer Center and the Department of Radiation late intensity, delivering varying ous lesions and better define the
Oncology and Molecular Radiation Sciences
have a long and proven history of leading
degrees of energy based on the specific anatomy of the tumor and its response
cancer research and advancing cancer makeup of the tumor, adjusting to to radiation treatment.
care. This expertise sets the Johns Hopkins differences throughout a tumor to Another advanced technology, called
Proton Therapy Center apart. provide the right amount of energy respiratory gating, tracks motion in
to every area. the lung and stops the beam if the
THE JOHNS HOPKINS KIMMEL CANCER CENTER 7
beam and tumor lose alignment due to The Proton Therapy Center also imaging makes our proton therapy the
motion caused when patients breathe. has magnetic resonance, or MR, and most precise of any available today.
The beam works when it is lined up CT imaging, as well as a new type of
with the tumor and stops when it is CT scan called dual energy CT, which Proton for Pediatrics
not lined up. The Johns Hopkins Pro- provides detailed information on the One area where most experts agree the
ton Therapy Center will be conducting specific makeup of the area around the benefit has clearly been demonstrated
research on the use of gating in treat- tumor. This advanced and unmatched is in pediatric patients.
ment planning. Matthew Ladra, M.D., M.P.H.,
director of pediatric radiation oncology
“When children get exposed to radiation at at Sibley Memorial Hospital, earned a
a young age, they are at much higher risk proton therapy-specific fellowship
mainly focused on pediatrics.
for issues down the road when they are “When children get exposed to radi-
ation at a young age, they are at much
long-term survivors. Our goal is to radiate higher risk for issues down the road
what’s supposed to be radiated and leave when they are long-term survivors,”
says Ladra. “Our goal is to radiate
everything else alone. Proton therapy helps what’s supposed to be radiated and
us do that.” leave everything else alone. Proton
therapy helps us do that.”
MATTHew LADRA THIS PHOTO wAS TAken BefORe
“WE ARE BRINGING
THe COvID-19 PAnDeMIC.
WORLD-CLASS
CANCER CARE AND
CUTTING-EDGE
RESEARCH TO
PATIENTS HERE AND
AROUND THE WORLD.”
A unique partnership with Children’s
National Hospital that began in 2016
creates one of the largest pediatric
radiation oncology programs in the
country. The patient volume and
clinical collaborations, including joint
clinical trials and research initiatives
with the National Institutes of Health,
are expected to speed clinical discovery.
Watch “We Speak Proton”:
INNOVATION
(Left) Heng Li, Ph.D., http://bit.ly/2COSKAM
Chief Proton Physicist,
(Right) John Wong, Ph.D.,
Director of Medical Physics
8 T HE JOHNS HOPKINS KIMMEL CANCER CENTER
NEWS & UPDATES
TA RG E T E D T H E R A P I E S
IMMUNE THERAPIES
A DVA N C E D T E C H N O LO G I E S
O N G O I N G R E S E A RC H
C A N C E R T R E AT M E N T S
AkiLA VisWAnATHAn nAMeD
was her motivation for developing the
DIReCTOR Of RADIATIOn procedure.
OnCOLOgy AnD MOLeCuLAR
RADIATIOn SeRvICeS “I want women who have inoperable
cancer that is limited to the gynecologic
area to be cured of their cancer,” she says.
Women who have surgery for cancer
often lose their entire gynecologic tract,
including the cervix, she explains.
Brachytherapy preserves these organs,
which is particularly important for
young women.
The procedure was first done with
CT guidance, but Viswanathan says
studies show better cancer control and
survival rates with MR guidance, so
now she only performs MRI-guided
brachytherapy.
“Tumors can be very large and can
extend into the bladder and rectum,
and MR allows us to see all of the places
the tumor is located,” she says. The
types of MR technology she uses are
unique. Working with a team of physi-
AN ORGAN-SPARING OPTION
cists who write special codes to direct
the MR scanner, she can look inside a
tumor and provide a variety of details
FOR GYNECOLOGIC CANCERS
not available with traditional MRI.
Outcomes are excellent for cervical
cancer and recurrent uterine, vulvar
and vaginal cancers. Viswanathan says
In July 2020 Akila Viswanathan, M.D., Center location in East Baltimore, she published data shows MR-guided
M.P.H., was named Director of the brought the therapy to its Sibley Me- brachytherapy survival rates of over
Department of Radiation Oncology morial Hospital location. 90%. As a result, Viswanathan is in
and Molecular Radiation Sciences. Using active magnetic resonance demand, seeing about 300 patients a
While serving as Director of Radiation imaging (MRI) guidance, physicians year from all over the world.
Oncology for the National Capital Region, insert several hollow catheters into the On the research side, she has
Dr. Viswanathan led the October 2019 tumor. Radioactive seeds about the size studied combining drug therapies with
opening of the Johns Hopkins Proton of a grain of rice tethered together by a brachytherapy, including using drugs
Therapy Center, one of the largest and long thread are inserted into the that block blood supply to tumors and
most advanced centers in the U.S. catheters and remain there for about ones that boost the immune response.
As a leader in the field of radiation 10 minutes, providing a rapid but high She is also collaborating with gene
oncology, she has developed numerous dose of radiation to cancer cells. A sequencing expert Srinivasan
clinical innovations, published more computer controls the insertion and Yegnasubramanian, M.D., Ph.D., on a
than 200 articles and chapters and lec- removal of the seeds, ensuring a pre- precision medicine approach. By
tures nationally and internationally. cise dose throughout the tumor. sequencing the genome of tumor
Viswanathan was the first in the U.S. “Gynecologic cancers can grow fast samples obtained at biopsy, she can
to use real-time magnetic resonance- and require a very focused high dose to begin to define biomarkers that distin-
guided interstitial brachytherapy for attack the tumor,” Viswanathan explains. guish otherwise similar-looking
the treatment of gynecologic cancers. The entire outpatient procedure cancers. Information like this can
After establishing a program at the takes just a few hours and provides a help better guide treatment.
main Johns Hopkins Kimmel Cancer lifetime of benefit to patients. That
T HE JOHNS HOPKINS KIMMEL CANCER CENTER 9
Spacer Shields Nearby
NEW FUND HONORS THEODORE DEWEESE Organs in Pancreatic
Cancer Treatment
BY ADVANCING CANCER RESEARCH JOHNS HOPKINS researchers are test-
ing whether a biodegradable hydrogel
with the consistency of toothpaste
A LEAD GIFT from Erwin and Stephanie more information on their research.) could help protect the duodenum (the
Greenberg established the Theodore L. “Ted is a remarkable physician, head of the small intestine) during ra-
DeWeese, M.D., Award for Innovative mentor and human being, and he was diation therapy for pancreatic cancer.
Cancer Research in the Department instrumental in the creation of the If successful, the spacer could help
of Radiation Oncology and Molecular Department of Radiation Oncology solve a problem in pancreatic cancer,
Radiation Sciences. The fund honors and Molecular Radiation Sciences. His for which advanced radiation thera-
DeWeese’s commitment to innovative heart is in radiation oncology, where DIng
pies are increasingly
and high-value patient care and expert he has established a culture of excel- used to target locally
research, and will advance cancer lence in patient care and discovery. advanced cancer that
research by supporting projects across Our hope is that many others will join cannot be surgically re-
departments and specialties. us and the fund will grow, providing moved. These therapies
An annual award of up to $100,000 new opportunities for investigators to work best when clinicians
will be presented to one or more emulate Ted’s commitment and advance can increase the radiation dose over
individuals committed to innovative the field in his honor. It gives all of us time, but there is a limit to how much
research in radiation oncology and an opportunity to participate in the radiation can be used before “spilling
the radiation sciences, with the goal of discovery process,” say Erwin and over” to harm healthy tissue.
better serving patients. The Greenbergs Stephanie Greenberg. “It’s important to deliver a high
asked DeWeese to direct the fund, giv- DeWeese, who oversaw radiation amount of radiation to the tumor to
ing him discretion to select recipients oncology gaining departmental status achieve a good outcome,” says Kai
from throughout The Johns Hopkins in 2003, served as director of the Ding, Ph.D., assistant professor of
University, including medical students, department until 2018, when he was radiation oncology and molecular ra-
residents, fellows, physician trainees, named vice dean for clinical affairs. diation sciences, “but for the pancreas,
physics trainees, research scientists “I am incredibly appreciative and it’s difficult because the duodenum,
and faculty members, who are under- humbled by this honor,” says DeWeese. the stomach and the liver are all close
taking novel and inventive approaches “Obtaining funding for novel ideas is to the pancreas. We can still deliver
in cancer research and the treatment difficult, particularly for our young radiation, but it’s not the level of
of cancer. investigators. This award will allow radiation that we want.”
The inaugural recipients of the award rapid pursuit of ideas and concepts The hydrogel separates the two
are Ana Kiess, M.D., Ph.D., and Amol that, if proven, can be leveraged into organs by about 8 millimeters. “This
Narang, M.D. (See pages 13 and 14 for larger, competitive grants.” extra space allows the radiation to fall
off so that the duodenum receives a
much smaller dose,” he says.
A multi-institution clinical trial for
patients with locally advanced pancre-
atic cancer and patients with border-
line resectable pancreatic cancer —
pancreatic tumors that have attached
to nearby blood vessels, making surgi-
cal removal of the entire tumor diffi-
cult or even impossible — has started
to further study the biodegradable
spacer gel, which he says disappears
from the body in about six months.
Hydrogel spacers are most com-
monly used in the treatment of prostate
cancer, but Ding says they are being
studied in liver cancer, treatment for
From left: amol narang, M.D., Stephanie and which also has the potential to affect
Erwin Greenberg, theodore DeWeese, M.D.,
ana Kiess, M.D., Ph.D., akila Viswanathan, M.D., M.P.H.
THIS PHOTO wAS TAken BefORe nearby organs in the crowded abdomen,
THe COvID-19 PAnDeMIC.
in gynecologic cancers in the pelvis,
and head and neck cancers to shield
saliva-producing glands.
INNOVATION To develop a new type of therapy called nanoParticlE HyPErtHErMia, radiation oncology researcher Robert ivkov, Ph.D., is collaborating with a multi-institutional and multispecialty team of researchers, including Johns Hopkins veterinarians Dara kraitchman, v.M.D., Ph.D., and Rebecca krimins, D.v.M; radiation oncologist Lawrence kleinberg, M.D.; medical physicist kai Ding, Ph.D.; and radiation therapists and Mount Sinai neurosurgeons Costas Hadjipanayis, M.D.; and Alexandros Bouras, M.D. TURNING UP THE HEAT ON TUMORS Robert ivkov
THE JOHNS HOPKINS KIMMEL CANCER CENTER 11
Robert Ivkov, Ph.D., wants to enlist iron disease, and in particular, we will be advantage of magnetic hyperthermia.
oxide nanoparticles, each about a mil- asking, is this combination curative, When combined with an image of the
lion times smaller than a human cell, will it reduce tumor size, will it reduce nanoparticle distribution in the tis-
as tiny but potent weapons in the treat- tumor recurrence, what are the side sues, Ivkov and his team are confident
ment of tumors. Injected as part of a effects and toxicity?” says Ivkov. “The that mathematical models of tissue
saline or water solution directly into results from mouse models have heating and heat transfer can provide
tumor tissue, the nanoparticles can be shown significant promise to treat the needed guidance to adjust magnetic
heated using oscillating magnetic fields glioblastoma, but mouse models can field controls to manage the heat ther-
produced by a device developed in only get us part of the way,” adds Ivkov. apy. “We need to reliably achieve a
Ivkov’s lab. The heat stresses the tumor By treating dog patients, the research minimum dose in as large a volume of
cells and should make them more vul- team hopes to develop techniques to the tumor as possible without over-
nerable to other cancer therapies, he says. improve treatments for both human heating normal tissues, and that’s the
“By heating the tumor this way, we and animal patients suffering from challenge,” Ivkov explains. Ivkov and
could actually make a dose of radiation deadly brain tumors. his team integrate materials science,
or chemotherapy more effective,” says physics and engineering with medicine
Ivkov.
Nanoparticle hyperthermia is unlikely INJECTED AS PART OF A to develop new approaches for difficult
diseases such as glioblastoma.
to be a stand-alone treatment, Ivkov
says, but paired with other therapies, SALINE OR WATER SOLUTION The nanoparticles also can be deliv-
ered intravenously, tagged with small
DIRECTLY INTO TUMOR TISSUE,
it could address an unmet treatment molecules or antibodies that change
need for some inoperable brain and the way in which the nanoparticles in-
HEATED NANOPARTICLES
pancreatic cancers. teract with the body’s immune system.
“This is a potential tool that gives This systemic use of nanoparticles is
clinicians and their patients some more suited to metastatic cancer, the
measure of improvement in control-
ling that large or advanced local
CAN STRESS TUMOR CELLS researchers say. Already, Ivkov and
others observed that nanoparticles
tumor,” he notes. “Or it could help in
managing side effects by allowing the
AND MAKE THEM MORE delivered in this way can stimulate the
body’s immune system, triggering an
clinician to treat the tumor with a lower
dose to help reduce the issues with toxi- VULNERABLE TO OTHER anti-cancer immune response. Preethi
Korangath, a member of Ivkov’s
city, or with the same doses to make the
radiation much more effective.” CANCER THERAPIES. research team, has recently discovered
that antibody-labeled nanoparticles
For more than five years, Ivkov has are preferred by immune cells residing
been working with colleagues at the One particular challenge with direct in cancer tumors. This finding offers
Johns Hopkins Kimmel Cancer Center delivery of nanoparticles is tracking new potential to attack other cells that
and the Icahn School of Medicine at where nanoparticles go when they are support the growth of the cancer cells.
Mount Sinai to refine and test the injected. Imaging the nanoparticles in This discovery was made with initial
nanoparticle heating technique on tissues has proved beneficial from pre- research funding provided by the Jayne
mouse models of glioblastoma to vious work conducted by Ivkov and his Koskinas Ted Giovanis Foundation for
determine how heated nanoparticles radiology colleagues. They discovered Health and Policy (JKTG Foundation).
could act as a radiation-enhancing that the nanoparticle solution doesn’t A new round of funding from the JKTG
agent. He and his collaborators applied spread uniformly through the disor- Foundation enabled Ivkov, Lombardi
for National Cancer Institute funding ganized tissue of a tumor, which can lead Comprehensive Cancer Center breast
to study the treatment in glioblastoma to difficulties for treatment. cancer researcher Robert Clarke, Ph.D.,
in veterinary dog patients. They hope This uneven distribution means that and Johns Hopkins veterinary pathol-
to begin treating canine patients when it’s time to heat the nanoparticles, ogist Kathleen Gabrielson, D.V.M.,
within the next two years at the Johns there are inevitable “hot” and “cool” Ph.D., study this immune response in
Hopkins Center for Image-Guided spots in the tumor. The researchers more detail to understand how it could
Animal Therapy and in the Department are experimenting with ways to heat be strengthened or prolonged and
of Radiation Oncology and Molecular the particles quickly and then reduce what features of the nanoparticles are
Radiation Sciences with a novel the temperature to allow the heat to responsible for inducing these effects.
combination of surgery, nanoparticle dissipate through the tumor. Adjusting “The nanoparticles are about the same
hyperthermia and chemoradiation. the heat output of the nanoparticles size as pathogens like viruses, and it’s
“We want to study all aspects of is accomplished remotely by simply possible that our immune systems
nanoparticle hyperthermia with radia- adjusting the power of the magnetic have evolved to pay attention to foreign
tion in a spontaneous disease model field device at the control panel. Ivkov bodies that are in a specific size range,”
that more closely resembles human claims this is a key Ivkov says.12 T HE JOHNS HOPKINS KIMMEL CANCER CENTER
INNOVATION
Molecular radiation sciences researchers
discover a new vulnerability in cancer cells.
MOLECULAR RADIATION SCIENCES related to the majority of cancer muta- “The challenge is to cross the ‘Valley
researchers discovered a new vulnera- tions identified to date. The other two of Death,’ to move the lab discoveries
bility in cancer cells that polymerases, however, provide essen- to the clinic,” says Laiho. “The process
provides an opportunity tial molecular tools that help make the is costly and complex. It needs a team
to develop new cancer actual proteins. “Pol 1 is fundamentally of experts, and I truly appreciate the
drugs. Marikki Laiho, important for every cell, so it has not opportunity to align with collaborators
M.D., Ph.D., the Willard been considered an actionable target that share the same mindset and goals
and Lillian Hackerman for cancer therapy. If you hit it, the to push early-stage research targets
Professor of Radiation Oncology and thought was that you would harm every forward,” says Laiho. She says her
director of molecular radiation sciences, cell, not just cancer cells,” says Laiho. team, medicinal chemist James Barrow
discovered new drug-like molecules Laiho proved that was not the case at the Lieber Institute, and Kimmel
that effectively killed cancer cells. after developing a drug that targets Pol Cancer Center researchers provide
Researchers found that the molecules 1 and studying it in the laboratory. She expertise and support and have con-
specifically blocked RNA polymerase 1 found that cancer cells rely on it more ducted the extensive work required to
(Pol 1) and that cancer cells rely on a than normal cells, so it was possible to develop the Pol 1 inhibitors into an in-
Pol 1 pathway much more than normal interfere with the pathway without vestigational new drug. This is a critical
cells. This discovery led to a new op- causing excessive damage to normal step in overcoming a common barrier
portunity for a targeted therapy that cells. “Cancer cells can’t survive with- to advancing promising investigator-
disrupts cancer cells with little harm to out this program. They can’t function,” initiated drug discoveries and to
healthy ones. The drug could also aug- says Laiho. “Just as important, however, initiating the first clinical trials.
ment the benefits of radiation therapy. normal cells don’t take much notice.” “Dr. Laiho’s promising research may
Cells have three main ways — Pol 1, This research was propelled by prove to be a transformational cancer
2 and 3 — to read the instruction man- funding from foundations supporting treatment. We’re excited about this
ual that is our DNA and convert those cancer research, the National Insti- progress and new opportunity,” says
instructions into protein-based actions tutes of Health, and recently, Bluefield Akila Viswanathan, M.D., M.P.H.,
that are dictated by genes. Pol 2 is stud- Innovations, a collaboration between Director of Radiation Oncology and
ied most in cancer because it executes healthcare investment management Molecular Radiation Sciences.
the primary program that orchestrates firm Deerfield Management and The
the expression of defective proteins Johns Hopkins University.
Discovery Leads to New Clinical
Trial for Prostate Cancer
ANDROGEN SUPPRESSION is a widely tion of the DNA, says radiation oncolo- Ph.D., and Theodore DeWeese, M.D.,
used tool in the fight against prostate gist and prostate cancer expert Daniel to turn this cancer vulnerability into a
cancer. Prostate cancer cells are stimu- Song, M.D., who is collaborating with new treatment.
lated by male hormones called androgens, Srinivasan Yegnasubramanian, M.D., As the DNA is reorganized, it is cut
such as testosterone, and suppressing or in many places, Song explains. These
blocking androgens can starve cancers breaks, known as double-strand breaks
of these hormones and help kill them. because they go through the double helix
However, when cells that have been that characterizes DNA, are often too
starved of androgens are later exposed difficult for cells to repair, and so the
to them again, it triggers a cascade of cells die. Building upon research in
events. One of these is the reorganiza- SOng DeweeSe yegnASuBRAMAnIAn mouse models by radiation oncologistT HE JOHNS HOPKINS KIMMEL CANCER CENTER 13
and prostate cancer expert DeWeese and
prostate cancer and molecular biology
Radiation Therapy help tumors shrink away from these
vessels, making surgery possible for
expert Yegnasubramanian, Song is con-
ducting a clinical study funded by The
Can Help Make more patients.
“Surgery offers patients the only
Patrick C. Walsh Prostate Cancer Re- Cancers Operable chance for a cure, and patients who
search Fund that uses the double-strand undergo successful surgeries live
breaks to augment radiation therapy. Amol Narang, M.D., is focused on longer on average as compared with
“The androgen receptor triggers advanced technologies and discoveries those who can’t have their tumors
DNA enzyme activity, including an that allow for the delivery of higher and removed,” says Narang. “Patients with
enzyme called topoisomerase 2-beta, more precise doses of locally advanced and borderline re-
which cuts DNA. We believe giving radiation to pancreatic sectable cancers who undergo success-
radiation therapy on top may kill cancers, with the aim to ful removal of their tumors experience
prostate cancer cells better than radia- improve survival. survival that is similar to patients who
tion alone or androgen receptor agonist One approach allows don’t have blood vessel involvement
stimulant therapies alone,” says Song. surgeons to successfully and go straight to surgery.”
remove more cancers that were previ- There is also evidence that high
ously thought to be inoperable, which is doses of radiotherapy may make cancer
Prostate cancer cells are necessary for patients to have a chance cells more responsive to subsequent
stimulated by male hor- to get well. treatment with immunotherapy.
mones called androgens, Building upon research using a very Radiation damage to the tumor may
precise, high-dose form of radiation make it more recognizable to the im-
such as testosterone, and therapy known as stereotactic ablative mune system and may prime patients
suppressing or blocking radiotherapy, Narang can get high doses to respond better to new drugs that
androgens can starve of radiation to pancreatic tumors that give the immune system an upper
have attached to nearby blood vessels, hand on cancer. The potential of this
cancers of these hormones a situation that makes surgical removal immune-boosting component in
and help kill them. of the entire tumor difficult or even pancreatic cancer is currently the
impossible. These cancers are referred focus of clinical trials.
The radiation treatment comes in to as borderline resectable (operable)
the form of brachytherapy, a procedure or locally advanced cancers. “New technologies are
in which radioactive seeds are injected “There are a number of key blood allowing us to safely get
into prostate tumors to kill cancer cells. vessels that course near the pancreas,
Song explains that patients will be and as pancreatic cancers abut, encase
higher doses of radiation
on androgen suppression therapy for or occlude these vessels, it becomes to pancreatic tumors,
one month leading up to brachytherapy. harder and harder for surgeons to providing more patients
The night before brachytherapy, successfully remove cancers without
patients will take a single dose of the leaving cancer cells behind,” explains
with an opportunity for
drug flutamide, which is FDA-approved Narang. Surgeons must peel the cancer a surgical cure.”
for prostate cancer but also has a para- away from these delicate vessels,
doxical effect of partially stimulating adding to the complexity of the already Narang says improvements in endo-
the androgen receptor. Laboratory stud- complicated surgery and increasing scopic procedures are allowing radia-
ies have shown that giving flutamide the chances that a few cancer cells will tion oncologists to deliver radioactive
with radiation is more effective at be left behind, which can later result in treatment internally to pancreatic
killing prostate cancer cells compared the cancer recurring or spreading. tumors. Using endoscopy-guided
with either one alone. Giving flutamide Stereotactic ablative radiotherapy ultrasound to direct the placement
before treatment in patients who are is focused radiation that reduces expo- of this treatment, Narang can inject
on androgen suppression therapy may sures to surrounding tissue and organs, radioactive material directly into the
make brachytherapy work even better. and makes it possible to deliver higher pancreas tumor, which may allow an
“Cancer cells already deprived of doses of radiation to tumors over a increased radiation dose to be directly
androgen that then get restimulated with relatively short period of time: five days delivered to the tumor without harming
flutamide respond with more DNA versus six weeks with conventional other tissues and organs.
breaks,” Song explains. radiation therapy. Combining modern “New technologies are allowing us
A 24-patient clinical trial is planned combination chemotherapy and to safely get higher doses of radiation
to confirm that the DNA breaks observed stereotactic ablative radiotherapy to pancreatic tumors, providing more
in animal studies also occur in patients in patients with pancreatic cancers patients with an opportunity for a
receiving flutamide. that have attached to blood vessels can surgical cure,” says Narang.14 THE JOHNS HOPKINS KIMMEL CANCER CENTER
RADIATION
other hospitals and clinics that do not heading studies with Martin Pomper,
have the infection control capabilities M.D., Ph.D., an expert in transforming
to care for COVID-positive patients. imaging agents into therapeutic agents.
TREATMENT
I am pleased to report that our Although many are familiar with
safety precautions and frequent radiation therapy that uses beams to
COVID testing have kept our patients deposit energy that kills the cancer
and dedicated healthcare staff safe. cells, radiopharmaceuticals are
DURING THE
radiation therapy in medicine form.
Kiess and Pomper are adapting a
W E B E X C L U S I V E : Listen to radiolabeled agent that is given at
PANDEMIC
On Target with Dr. Akila Viswanathan very small doses for diagnostic
who delves into cutting-edge science imaging PET scans for therapy.
with her team of radiation oncologists. The agent is used in imaging to
https://hopkinskimmel.libsyn.com/ make cancer cells visible, but when
wAng category/Dr+Akila+Viswanathan used at a higher dose and targeted
A message from Dr. Akila Viswanathan, directly to cancer cells, it can also kill
Director of Radiation Oncology and the cancer. Kiess and Pomper use
Molecular Radiation Sciences prostate-specific membrane antigen
(PSMA) as the delivery method for the
kIeSS
THE SAFETY OF our cancer patients radiolabeled drug. When the drug is
throughout the pandemic has been and injected via IV, it automatically travels
continues to be our top priority. We to PSMA-expressing cells.
work closely with our colleagues in epi- “PSMA is present in the normal
demiology and infection control to im- prostate, present in the brain, the kid-
plement safety practices. ney, salivary glands and the intestines,
Our radiation oncology faculty, but it’s expressed much higher in
nurses and staff received extensive prostate cancer cells,” Kiess says. Her
COVID-19 preparation and training. first focus was to make sure they could
When possible, virtual telemedicine
deliver the drug to cancer cells without
appointments are offered to patients.
harming normal cells. The drug will go
For patients who must come to us in
into any cell that expresses PSMA.
person for treatment or other care, we
Prostate cancer cells express 100 times
implemented rigorous COVID-19 pre-
more PSMA than kidney and salivary
cautions at our front doors and in our
cells, and as an added protection, Kiess
waiting rooms and clinical treatment
areas. and collaborators worked with chemists
Every patient receives a COVID test, to modify the drug and make it more
so that we can attend to patients who specific to tumor cells and less likely
may need to pause treatment as they to go into normal cells.
recover from a COVID infection. Pa- The drug, called LU-PSMA-R2, will
tients who are experiencing symptoms soon be studied in a multicenter inter-
or have been admitted to the hospital national clinical trial in patients with
receive a COVID test. advanced prostate cancer. Findings
We established biocontained simu- from Kiess’ laboratory research that
lation and treatment rooms for adult served as the foundation for the clini-
and pediatric patients at our East cal trials were published in the Journal
Baltimore campus. These rooms are Radiation Therapy of Nuclear Medicine in 2017 and won the
Editor’s Choice Award.
uniquely set up with special air flow
and filtering to care for patients with
in Drug Form PSMA is also present in kidney cancer,
infectious diseases, keeping them safe A TEAM of radiation oncologists, radio- glioblastoma brain cancer, pancreatic
and cared for while preventing the chemists and biologists are collaborat- cancer, and some head and neck cancers,
spread of the infection to other pa- ing to develop radiolabeled drugs as a opening the door for the drug to be used
tients. During this time of pandemic, new way of delivering cancer cell-killing for other cancers if the prostate cancer
we are providing service and aid to radiation to prostate cancer cells. Radi- trials are successful.
patients throughout our Maryland and ation therapy comes in many different
Washington, D.C. communities, caring forms, explains radiation oncologist
for many patients transferred from Ana Kiess, M.D., Ph.D.,who is spear-Corey’s Story
CARE
OVERCOMING A SPINAL TUMOR
“JOHNS HOPKINS IS
COMPREHENSIVE.
DRS. REDMOND AND
LO COLLABORATE ON
A DAILY BASIS. ALL
THE DOCTORS I NEED
ARE RIGHT THERE.”
CORey LIDOnne
WHEN 32-YEAR- OLD Corey LiDonne isn’t busy at his show him exactly where the tumor was and discuss
job at Facebook, the electrical engineer-turned- their plan to remove it.
construction manager can often be found outdoors Despite the rare nature of chordoma, the Kimmel
in Oregon skiing, hiking along the coast or camping Cancer Center treats a relatively large number of
on the beach while taking in the surrounding bluffs patients with this type of cancer, says Redmond,
and cliffs, a backdrop of which he never tires. But who leads the spine radiosurgery program. This
recently, Corey had to interrupt his busy lifestyle larger caseload gives Redmond and the team oppor-
to confront a surprising diagnosis. tunities to use therapies that other hospitals may
In February 2019, he was diagnosed with sacral not have the experience to employ. Redmond says
chordoma, an aggressive but slow-growing form she uses stereotactic ablative radiation therapy,
of cancer so rare it’s detected only in about one in 1 for instance.
million people per year and just 300 patients in the “Stereotactic radiation gives a high dose of
ReDMOnD United States annually. Corey wasted radiation to the tumor, keeping areas around it
no time gaining access to the best at low dose. So far, we’ve had excellent outcomes
treatment he could find. From his with minimal side effects,” says Redmond.
home on the West Coast, he researched About a month after his diagnosis, Corey under-
his options. Within a week, he con- went stereotactic radiation: five 90-minute sessions
tacted Johns Hopkins and got on a on consecutive days. He says he experienced only
plane headed to the Kimmel Cancer Center for a slight grogginess and nausea during treatment.
consultation with neurosurgeon Sheng-Fu Larry About a month after the radiation, he had surgery
Lo, M.D., radiation oncologist Kristin Redmond, at Johns Hopkins to remove the tumor.
M.D., and other experts in the Spinal Tumor As his life has taken this unforeseeable turn, Corey
Multidisciplinary Program. finds reassurance in the stability of his medical team.
Corey says the easy accessibility to members of “Johns Hopkins is comprehensive. Drs. Redmond and
Johns Hopkins’ treatment team reaffirmed his deci- Lo collaborate on a daily basis. All the doctors I need
sion to head east. The multispecialty team of experts are right there,” says Corey, who has his sights set on
explained images of Corey’s MRI and CT scans to returning to his active lifestyle in Oregon.Thank You for Your Support!
Sibley Memorial Hospital and Johns Hopkins Medicine are grateful
to the Morris and Gwendolyn cafritz Foundation and other gener-
ous donors for their support of the Johns Hopkins Proton therapy
center. Philanthropy has provided support for these new facilities
and critically important equipment, physician training programs,
and groundbreaking research programs. Most importantly, donor
support allowed us to expand treatment options for cancer patients
in the Washington, D.c. region and beyond, providing the most
advanced pencil beam proton therapy technology available.
Help Us Make To make your donation online
a Difference
hopkinscancer.org and click
“Make A Gift”
Each contribution to the Johns Hopkins
Kimmel Cancer Center makes a differ- To mail your donation
ence in the lives of cancer patients here Johns Hopkins Kimmel Cancer Center
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Our physician-scientists are Baltimore, MD 21202
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donation will support patient care and Office
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