Cancer Advances Harnessing the Power of Precision Oncology - Ranked No. 5 in America for cancer care by U.S. News & World Report - Cleveland Clinic
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Cancer Advances Cleveland Clinic Cancer Center | W i n t e r 2019
Harnessing the
Power of Precision
Oncology
Ranked No. 5 in America for cancer care by U.S. News & World Report.
Advancing
Dear colleagues,
Welcome to this issue of Cancer Advances. Our cover
story features a sampling of our work in genetics and
genomics, which is shifting the focus of questioning
Precision
in oncologic research and care from tumor location
to genetic mutation. Our researchers are approaching
questions of cancer genetics from across the continuum,
including detecting cancers at an earlier stage (p. 4), best
Oncology
practices in testing for non-small cell lung cancer (p. 6),
expanding the use of predictive assays (p. 7), treatments
targeting individual tumor DNA (p. 8) and a new National
Cancer Institute grant to study response prediction in
radiation oncology (p. 10).
Our leadership in developing the accreditation program
for rectal cancer (p. 22) and the continued relevance and
utility of the Khorana score (p. 14) showcase our ability to
from Risk Prediction
determine the line of inquiry at the national level.
Our multidisciplinary Sarcoma Program continues to
to Treatment Response
investigate better treatments for this rare cancer while
providing patients with a level of expertise matched by few
centers in the United States (p. 16). Our work on potential
new therapies for acute myeloid leukemia (p. 20) and
breast cancer (p. 13) demonstrates the promising results of
the continued pursuit of inquiry for our patients.
Finally, we demonstrate our ability to ask complex
questions with the work we’re pursuing on laser interstitial
therapy with colleagues in the Rose Ella Burkhardt Brain
Tumor and Neuro-Oncology Center (p. 24).
I hope this issue of Cancer Advances sparks new insights
into your research and clinical questions, and I welcome
the opportunity to collaborate, to discuss new ideas and
to answer your questions, from bench research to clinical
trials to operations and strategies for optimal clinical
alignment. If we can help you with a patient’s care or a
clinical issue, please let me know.
Sincerely,
Brian J. Bolwell, MD, FACP
Chairman, Taussig Cancer Institute
Cleveland Clinic Cancer Center
bolwelb@ccf.org | 216.444.6922
On Twitter: @BrianBolwellMD
Cleveland Clinic Cancer Center | Care that’s personal. Research that’s revolutionary.
Cancers are increasingly seen as diseases of the genome. The characterization of
genetic and protein abnormalities now often determines how cancers are diagnosed
and treated. Precision oncology uses genetic information from an individual’s
Cleveland Clinic’s Charis Eng, MD, PhD,
cancer to determine the most effective treatment, and allows the use of an agent and former Vice President Joe Biden
targeted to that specific genetic abnormality. receive the 2018 Medal of Honor from the
American Cancer Society...11
This increasingly complex and variable picture of cancer further underscores the
need for innovative responses. Novel approaches are essential in every realm of
cancer care: genomic data collection and analysis; drug development; clinical trial Table of Contents
design; surgery, radiation and chemotherapeutics; cost reimbursement strategies;
ADVANCING PRECISION ONCOLOGY
research funding. Detecting Early-Stage Cancers
Circulating Cell-Free Genome Atlas Substudy
Fortunately, there is no shortage of inventive work underway when it comes to Demonstrates Project’s Potential to Map Cancer
cancer care. Cleveland Clinic’s strong clinical genomics program, housed in the Genetics...4
Center for Clinical Genomics, enhances the Cancer Center’s efforts to harness Best Practices in Testing
Next-Generation Sequencing Saves Time and
precision oncology for the benefit of patients. Many tumors undergo testing for Money for Treatment of Metastatic Non-Small Cell
genomic alterations, which are then reviewed by the Genomics Tumor Board, a Lung Cancer...6
regular meeting with various oncologists, translational scientists, pathologists and Expanding the Use of Predictive Assays
Multigene Assay Holds Prognostic Promise for
genetic counselors. Renal Cell Carcinoma...7
Experts then alert each patient’s physician to recommended, individualized Treatments Targeting Individual Tumor DNA
ALLELE: Guiding Glioblastoma Treatment with
treatment options, as well as to clinical trials for which the patient might be an Tumor Genetics...8
appropriate candidate. Every eligible patient is offered tumor genomic profiling.
Predicting Responses to Therapy
Abazeed Receives $2 Million Grant to Study Role
“It’s a very exciting time. Personalized cancer medicine is real,” says Brian Bolwell, of Genetic Composition in Predicting Radiation
MD, Chair of Cleveland Clinic’s Taussig Cancer Institute. “It’s not theoretic; it’s Therapy Efficacy...10
happening today in clinic. In some cancers for which we didn’t have much to offer
patients 10 to 15 years ago, we now have targeted therapies that are extending T-DM1 + Neratinib’s Safety and Efficacy
their lives and giving them a good quality of life as well.” in Women with Metastatic HER2+ Breast
Cancer...13
The following projects demonstrate a sampling of Cleveland Clinic’s expertise across The Khorana Score, 10 Years Later...14
the continuum, from prediction and prevention to diagnosis and treatment.
Sarcoma: Rare, Complex, Approachable with
Appropriate Care...16
VeloSano: 100% for the Cure...19
How Nucleophosmin Mutation Causes Acute
Myeloid Leukemia...20
Developing the National Accreditation Program for
Rectal Cancer...22
Tumor Ablation with Chemo-Radiotherapy
Consolidation Yields Rare Durable Remission of
Glioblastoma...24
New Staff...26
Chairman’s Q&A: Cultivating Emotional Intelligence
Through Asking Questions...26
Resources for Physicians...28
Cover image: The work of researcher and radiation
oncologist Mohamed Abazeed, MD, PhD, explores
whether the genetic composition of lung cancer cells can
predict response to radiotherapy. Dr. Abazeed recently
received a $2 million grant from the National Cancer
Institute for this research.
2 | 3 | clevelandclinic.org/cancer
CANCER ADVANCES WINTER 2019
A DVA N C I N G P R E C I S I O N O N C O L O GY
Detecting Early-Stage Cancers
Circulating Cell-Free Genome Atlas Substudy
Demonstrates Project’s Potential to Map Cancer Genetics
Dr. Klein is Chair of Cleveland Clinic researchers are helping NCT02889978 at a glance
Cleveland Clinic Glickman
build a database that could lead to the The observational study, funded by GRAIL Inc., has so
Urological & Kidney
Institute and Professor of development of a blood test for early-stage far enrolled > 11,000 of 15,000 planned participants (70
Surgery at Cleveland Clinic cancer and promises to shed new light on percent with cancer, 30 percent noncancer) in order
Lerner College of Medicine. the biology of cancer at its initial stages. to characterize the population variation in cancer and
He can be reached
Results of a preplanned substudy of this noncancer subjects. The research team will use deep
at kleine@ccf.org or
216.444.5591. multicenter clinical trial — the Circulating sequencing of cell-free nucleic acids in the blood, an
On Twitter: @EricKleinMD Cell-Free Genome Atlas (CCGA) — were emerging biomarker for earlier cancer detection, to
presented at the 2018 American Society of develop a detailed atlas of cancer genetics.
Clinical Oncology (ASCO) meeting.
The Center for Clinical Genomics team, along with
primary investigators Eric A. Klein, MD, Chair of
Cleveland Clinic Glickman Urological & Kidney Institute,
and Mikkael Sekeres, MD, MS, Director of Cleveland
Clinic Cancer Center’s Leukemia Program, will help
recruit more than 1,000 Cleveland Clinic patients over
the age of 20.
“The complex nature of cancer makes it difficult to
identify biomarkers for detection of early-stage cancer
before symptoms appear,” says Dr. Sekeres. “The CCGA
study will expand our knowledge about genomic pro-
files in cancer patients.”
Substudy methods and results
The preplanned substudy of 1,627 participants collected
blood from 878 participants with newly diagnosed,
untreated cancer (20 tumor types, all stages) and 749
participants with no cancer diagnosis (controls) for
plasma cell-free DNA (cfDNA) extraction. The team
performed three prototype sequencing assays: paired
cfDNA and white blood cell (WBC) targeted sequenc-
ing (507 genes, 60,000X) for single nucleotide variants/
indels, cfDNA whole genome bisulfite sequencing (30X)
for methylation, and paired cfDNA and WBC whole-
genome sequencing (30X) for copy number variation.
WBC sequencing identified the contribution of clonal
hematopoiesis.
Cleveland Clinic Cancer Center | Care that’s personal. Research that’s revolutionary.
CLEVELAND CLINIC CANCER CENTER | CANCER ADVANCES
Dr. Sekeres is Director of Cancer Advances provides information from
Cleveland Clinic Cancer Cleveland Clinic cancer specialists about
Center’s Leukemia innovative research and diagnostic and
Program and Professor management techniques.
of Medicine at Cleveland Please direct correspondence to:
Clinic Lerner College of Taussig Cancer Center / CA
Medicine. Cleveland Clinic
9500 Euclid Ave.
He can be reached at Cleveland, OH 44195
sekerem@ccf.org or
Cleveland Clinic Cancer Center annually serves
216.445.9353.
thousands of cancer patients. More than 450
On Twitter: clinicians, scientists and other cancer specialists
@MikkaelSekeres are committed to researching and applying the
latest, most effective techniques for diagnosis
and treatment to achieve long-term survival and
improved quality of life for all cancer patients.
Cleveland Clinic Cancer Center is part of
Cleveland Clinic, an independent, nonprofit,
multispecialty academic medical center.
Cancer Advances Medical Editor
Brian I. Rini, MD, FACP
Director, Genitourinary Cancer Program
Results from this first set of patients demonstrate that:
Managing Editor
• Strong biological signals are present in unscreened Deborah Booth Summers
cancers that are typically diagnosed at late stages. Designer
Amy Buskey-Wood
• Signals correlate highly across assays. With specificity Photography
set at 98 percent, sensitivity ranged from 56 to 80 Russell Lee, Steve Travarca, Don Gerda, Yu
Kwan Lee, Annie O’Neill, Matt Kohlmann
percent for a wide range of early-stage (I-III) cancers,
many of which currently lack good screening tests.
Cancer Advances is written for physicians
“These exciting results suggest that these assays are and should be relied on for medical education
purposes only. It does not provide a complete
sensitive and specific ways of detecting a variety overview of the topics covered and should
of cancers at an early stage,” says Dr. Klein. “The not replace the independent judgment of a
physician about the appropriateness or risks of
results demonstrate the power of current sequencing a procedure for a given patient.
technology and add to the growing trend of
© 2018 The Cleveland Clinic Foundation
personalized cancer medicine.”
4 | 5 | clevelandclinic.org/cancer
CANCER ADVANCES WINTER 2019
A DVA N C I N G P R E C I S I O N O N C O L O GY
Best Practices in Testing
Next-Generation Sequencing
Saves Time and Money for
Treatment of Metastatic Non-
Small Cell Lung Cancer
Dr. Pennell is staff Biomarker-driven treatment strategies are advancing
in the Department of
for metastatic non-small cell lung cancer (mNSCLC). In
Hematology and Medical
Oncology and Associate the past two years, the number of biomarkers has grown
Professor of Medicine at from one to four and could increase to six or seven in
Cleveland Clinic Lerner the next couple of years.
College of Medicine.
He can be reached at This presents a challenge for physicians as well as
penneln@ccf.org or government and private insurance organizations: Does
216.445.9282.
it make sense not just medically but also economically
On Twitter: @n8pennell
to test for each biomarker sequentially or to perform for tests, unit costs and mNSCLC prevalence based on
one test — next-generation sequencing (NGS) — for a literature, public data and expert opinion. In addition,
complete picture of the cancer’s DNA? time to receive results and total cost (test plus rebiopsy)
were calculated for each modality and compared with
That was the question Nathan Pennell, MD, PhD, staff in
NGS.
the Department of Hematology and Medical Oncology,
and colleagues sought to answer by creating a decision The model estimated that for a hypothetical 1 million-
analytic model studying four genetic testing scenarios member insurance plan, 2,066 mNSCLC patients with
for patients with mNSCLC. Centers for Medicare & Medicaid Services (CMS) insur-
ance and 156 mNSCLC patients with private insurance
“Traditionally when we had one or two biomarkers, you
would need to be tested for genomic alterations. NGS
would do a test and then wait for the results. If it came
testing saves CMS payers between $1.4 and $2.1 million,
back positive, you would treat the patients, and if it
with proportionate savings for commercial payers. With
came back negative, you would do the next test,” says Dr.
NGS and hotspot panel testing, patients start therapy
Pennell, who presented the results of the model at ASCO
2.8 and 2.7 weeks faster than with the sequential and
2018.
exclusionary options, respectively. The authors con-
“But now that we have a minimum of four biomarkers, it cluded that NGS testing in mNSCLC patients saves time
has become more difficult to justify doing these tests and money for patients and payers, and more quickly
sequentially,” he says. “Not only does it take time to identifies the appropriate treatment for an individual
do each test, you start running out of tissue from their patient.
biopsy. So then you have to get a new biopsy to perform
Dr. Pennell says part of the impetus for creating the
more testing. And, of course, each test costs money.”
model was to help insurers understand that using NGS
Four testing approaches will save both time and money. “Historically, insurers
Dr. Pennell and his colleagues created a decision ana- have resisted covering new technology to do tests,” he
lytic model to illustrate which genetic testing approach says. “We wanted to illustrate that not only is this the
was better in terms of cost and time. The model had right thing to do because patients get timely results
four different testing arms, and the team built a variety to help guide treatment, but ultimately it will cost the
of measures into the model, including turnaround time insurers less.”
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A DVA N C I N G P R E C I S I O N O N C O L O GY
Expanding the Use of Predictive Assays
Multigene Assay Holds Prognostic Promise
for Renal Cell Carcinoma
Approximately 30 percent of patients with stage I-III RCC patients with stage I-III disease. Cleveland Clinic
renal cell carcinoma (RCC) will relapse. The lack participated in a second study to confirm the assay’s
of accurate methods for estimating the true risk of validity and provide the required level 1B evidence
Dr. Rini leads Cleveland
recurrence in RCC has made it difficult for clinicians needed for the assay’s inclusion in treatment guidelines.
Clinic Cancer Center’s
and patients to make informed decisions regarding Genitourinary Program
Study analyzes patient data
treatment options. Standard risk classification and is Professor of
The first validation study was based on an observa- Medicine at Cleveland
systems — tumor, node, metastasis (TNM) staging;
tional cohort of untreated stage I-III RCC patients.1 Clinic Lerner College of
Fuhrman grade and ECOG performance status — which Medicine.
The latest study analyzed primary RCC tumor tissue
analyze clinicopathologic parameters only, have limited He can be reached
from 212 participants, with a focus on 193 with stage
prognostic value. A new study validating a multigene at rinib2@ccf.org or
III RCC, from the randomized prospective trial S-TRAC 216.444.9567.
assay hopes to change that landscape.
(Sunitinib as Adjuvant Treatment for Patients at High On Twitter: @brian_rini
In other tumor types, such as breast, prostate and colon, Risk of Recurrence of Renal Cell Carcinoma Following
multigene assays that reveal unique tumor biology have Nephrectomy).2 In S-TRAC, one-year adjuvant treatment
been extensively validated and shown to provide prog- with sunitinib, a multitargeted kinase inhibitor, pro-
nostic, and sometimes predictive, information beyond longed disease-free survival versus placebo in patients
traditional parameters that can guide the selection of with locoregional, high-risk RCC following nephrec-
adjuvant therapy. tomy. Based on the trial results, the U.S. Food and Drug
Over the past decade, a 16-gene recurrence score (RS) Administration (FDA) recently approved sunitinib for
assay, consisting of 11 cancer-specific and five reference adjuvant treatment for this category of RCC patients.
genes, has been developed and validated in one study of With the introduction of kinase inhibitors like sunitinib
and the immune checkpoint inhibitor nivolumab, the
RCC treatment landscape has rapidly evolved over the
past decade. Having a validated multigene assay may
enable more astute selection of adjuvant therapy for
locoregional and metastatic RCC.
The recent study’s primary objectives were to validate
the prognostic ability of the RS assay to differentiate
recurrence risk in untreated RCC patients with
(continued on page 8)
References
1. Rini B, Goddard A, Knezevic D, et al. A 16-gene assay to
predict recurrence after surgery in localised renal cell
carcinoma: development and validation studies. Lancet
Oncol. 2015;16(6):676-685.
2. Rini BI, Escudier B, Martini JF, et al. Validation of the 16-gene
recurrence score in patients with locoregional, high-risk renal
cell carcinoma from a phase III trial of adjuvant sunitinib.
Clin Cancer Res. 2018;24(18):4407-4415.
CANCER ADVANCES WINTER 2019
A DVA N C I N G P R E C I S I O N O N C O L O GY
Treatments Targeting Individual Tumor DNA
ALLELE: Guiding Glioblastoma
Treatment with Tumor Genetics
(continued)
locoregional, high-risk T3, and to evaluate the potential Despite improvements in surgeries, medical
association between RS result and benefit from therapies and radiation, the outlook for patients with
sunitinib treatment. glioblastoma (GBM) remains dismal. Patients live an
average of just 15 months after being diagnosed with
Results validate prognostic value
this aggressive brain tumor.
The study showed that the RS assay was able to identify
patients with low and high risk of recurrence, based GBM’s bleak prognosis is due in large part to the
on overexpression of certain genes, and provide heterogeneous nature of the tumor’s DNA. Tumors
independent prognostic information beyond the often have unique genetic signatures, so what works
parameters of standard systems. The results were for one patient may not work for another. Researchers
prognostic for time to recurrence (TTR), disease- now are exploring whether targeting treatment based
free survival (DFS) and renal cancer-specific survival on an individual tumor’s DNA could result in better
(RCSS) in both the placebo and sunitinib arms. The outcomes for patients with GBM.
performance of the RS result in the placebo arm was “We’d like to know the genetic driver of the patient’s
similar to the first study with a hazard ratio (HR) for a tumor before we treat them,” says Manmeet Ahluwalia,
25-unit increase in RS result of 4.24 versus 3.91 for TTR MD, Director, Brain Metastasis Research Program,
and 7.21 versus 5.55 for RCSS. When the high and low Cleveland Clinic. “The genomics of glioblastoma are
groups were compared, the HR for recurrence was 9.18 very diverse, and if we use targeted therapy that focuses
in the placebo arm; interaction with RS results and on the genetic alterations of the tumor, the chances of
treatment was not significant. success increase.”
The assay has now been validated in more than 830 Dr. Ahluwalia and investigators from several leading
patients across RCC stages I-III. “The study confirmed institutions are part of ALLELE, a new consortium to
the prognostic value of the gene signature. Patients generate prospective clinical genomics and inform
will have more useful information to understand the treatment decisions in patients with GBM.
true risk of recurrence,” says Brian Rini, MD, lead study
author and Leader, Genitourinary Program, Cleveland Clinical trial with biomarker groups
Clinic Cancer Center. Patients enrolled in ALLELE undergo extensive genetic
testing to determine the feasibility of genotyping their
Next step: studying predictive value
tumors in a time frame that would support real-time
While the study showed that the RS assay was able use in clinical trials. So far, the researchers have
to predict recurrence, it did not include enough enrolled 46 patients with GBM at five sites. The median
samples to determine whether the assay could predict time between surgery and biomarker analysis comple-
the benefit of sunitinib treatment. The next step is tion was 51 days, a clinically acceptable timeframe for
applying the RS assay to a larger data set; conducting patients with newly diagnosed GBM.
another study is currently under consideration. “The
data indicate that the gene signature might have Of those 46 patients, 26 with MGMT-unmethylated GBM
predictive value,” says Dr. Rini. were subsequently enrolled in INSIGhT, a companion
randomized multiarm trial comparing the standard
of care, temozolomide, with three other experimental
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Dr. Ahluwalia is Director of Cleveland
Clinic’s Brain Metastasis Research
Program and Professor of Medicine
at Cleveland Clinic Lerner College of
Medicine.
He can be reached at ahluwam@ccf.org
or 216.444.6145.
On Twitter: @BrainTumorDoc
adjuvant treatments — CC-115, neratinib or abema- Hope for better outcomes
ciclib. Predefined biomarker groups EGFR, PI3K and INSIGhT, which is currently enrolling patients, will look
CDK-positive will be evaluated for their ability to predict at overall survival in the experimental arms compared
outcomes in each arm. with the standard temozolomide arm. It will also look
The first is the standard-of-care arm, in which patients at secondary incidence of treatment-emergent adverse
receive temozolomide orally on a daily dosing schedule events and progression-free survival.
approximately two to three hours before daily radio- Eligible patients must have evidence that their tumor
therapy. Temozolomide is administered post radiation MGMT promoter is unmethylated and must be immu-
for up to six cycles (five days/cycle). Radiation occurs for nohistochemically negative for IDH1 R132H mutations.
a maximum of 49 days. Traditionally, the use of temozolomide is associated
In the second arm, patients receive temozolomide with just a one-month survival benefit in these patients.
orally on a daily dosing schedule approximately two Hence researchers such as Dr. Ahluwalia are hope-
to three hours before daily radiotherapy. Patients ful that the tumor-DNA tailored trial may result in
receive abemaciclib post radiation in a twice-daily improved outcomes.
predetermined oral dose. Radiation occurs for a “We are hoping this precision medicine-based approach
maximum of 49 days. is more likely to be successful compared with treating
Patients in the third arm receive twice-daily oral dosing the whole group with one therapy in a heterogeneous
of CC-115 along with daily radiation for a maximum of tumor.”
49 days.
In the fourth arm, patients receive temozolomide orally
on a daily dosing schedule approximately two to three
hours before daily radiotherapy. Patients receive nera-
tinib post radiation in daily predetermined oral dose.
Radiation occurs for a maximum of 49 days.
8 | 9 | clevelandclinic.org/cancerCANCER ADVANCES WINTER 2019
A DVA N C I N G P R E C I S I O N O N C O L O GY
Predicting Responses to Therapy
Abazeed Receives $2 Million Grant to Study Role of Genetic
Composition in Predicting Radiation Therapy Efficacy
Dr. Abazeed is associate Researcher and radiation oncologist Mohamed Abazeed, across and within individual cancer types — had not
staff in the departments
MD, PhD, has been awarded a $2 million grant from the been studied on a large scale. In 2016, Dr. Abazeed’s
of Radiation Oncology and
Translational Hematology National Cancer Institute (NCI) to explore whether the lab published results of the largest profiling effort of
and Oncology Research, genetic composition of lung cancer cells can predict cancer cell survival after radiation, comprising a collec-
and Assistant Professor response to and perhaps guide strategy for radiotherapy. tion of 533 genetically annotated tumor cell lines from
of Medicine at Cleveland
Clinic Lerner College of
26 cancer types.1 Results showed significant biological
Dr. Abazeed’s overall objective for this award is to
Medicine. diversity in the survival of cancer cells after exposure
identify new genetic markers calibrated on the basis of
He can be reached at to ionizing radiation, and offered evidence that new
abazeem@ccf.org or
radiation therapy effectiveness, and new drug-radiation
genetic features regulating cellular response to these
216.445.0061. therapy strategies that more precisely and effectively
treatments can be identified.
On Twitter: target the most radiation-resistant lung tumors.
@mohamed_abazeed Dr. Abazeed’s new NCI-funded investigation aims to
“Current radiation therapy regimens use a one-size-
advance the clinical translation of a short list of the
fits-all approach, not taking into account the genetic
most important regulators of radiation resistance in
content of individual tumors,” says Dr. Abazeed. “There
lung cancer. The molecular pathways implicated in their
is an urgent need to identify genetic markers that can
studies are found in as many as approximately 30 per-
recognize tumors that are more or less likely to respond
cent of patients or as few as 7 percent. His preliminary
to radiotherapy and translate these markers for clinical
work suggests that specific mutations in these pathways
use. This more personalized approach not only can
confer a strong phenotype of radiation resistance in
improve treatment responses, but it can also potentially
cells, human-derived mouse xenografts and patients
reduce toxicity, resulting in an improved quality of life
with non-small cell lung cancer.
for survivors who receive these treatments.”
Dr. Abazeed’s profiling efforts have also demonstrated
Efforts thus far to predict the response to radiotherapy
that some mutations that cause resistance to radia-
have been limited in large part because the genetic fea-
tion can be subclonal. Dr. Abazeed contends that these
tures that regulate tumor survival — and their frequency
subclones can become dominant during the course of
radiation. This treatment-associated subclonal evolu-
tion may have significant implications for radiation’s
ability to completely eradicate tumors. On the basis of
these studies, Dr. Abazeed seeks to advance a genetically
guided radiosensitization strategy that makes tumor
cells more sensitive to radiation therapy.
“If these hypotheses are correct, our results will demon-
strate that radiotherapeutic sensitizers can be selected
based on both the identity and type of genetic altera-
tions identified in a patient’s cancer, prompting an evo-
lution in the use of radiation from a generic approach
to one that is guided by the genetic composition of
individual tumors,” adds Dr. Abazeed.
Reference
1. Yard BD, Adams DJ, Chie EK, et al. A genetic basis for the
variation in the vulnerability of cancer to DNA damage. Nat
Commun. 2016;7:11428.
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Dr. Eng Receives Prestigious Medal of
Honor from American Cancer Society
Charis Eng, MD, PhD, Chair of the Genomic Medicine Institute
and Director of the Center for Personalized Genetic Healthcare
at Cleveland Clinic, received the American Cancer Society’s
Medal of Honor, the organization’s highest award, on Oct. 18,
2018, in Washington, D.C. She was honored alongside four
others who also “have made advances of unique magnitude in About Dr. Eng
the understanding, diagnosis, treatment, cure and prevention
Dr. Eng grew up in Singapore and the United Kingdom and entered the University
of cancer and whose professional careers have engendered
of Chicago at age 16. After earning an MD and PhD there, she specialized in
widespread feelings of admiration and respect.”
internal medicine at Beth Israel Hospital in Boston and completed a fellowship
This year’s recipients include former Vice President Joe Biden. in medical oncology at Harvard’s Dana-Farber Cancer Institute. She then trained
Past recipients include former President George H.W. Bush, in clinical cancer genetics at the University of Cambridge and the Royal Marsden
Senator Ted Kennedy, cancer researcher Judah Folkman and NHS Trust, and completed postdoctoral research training in human cancer
U.S. Surgeon General C. Everett Koop. genomics at the University of Cambridge.
Dr. Eng, an internationally renowned pioneer in cancer genomic When she returned to Dana-Farber Cancer Institute in 1995, she was one of only
medicine, was honored for her clinical research, which has two formally trained clinical cancer geneticists in the U.S.
significantly improved patient outcomes.
Dr. Eng joined Cleveland Clinic in 2005, where she founded and leads the
“I am honored and humbled to receive this award,” she says. “To Genomic Medicine Institute and its clinical arm, the Center for Personalized
receive it on stage with the Honorable Joe Biden as well as Genetic Healthcare. She holds the Sondra J. and Stephen R. Hardis Endowed
Jennifer Doudna and Emmanuelle Charpentier, co-discoverers of Chair in Cancer Genomic Medicine and has published more than 500 peer-
CRISPR-Cas9 gene editing, is overwhelming.” reviewed articles.
Michael Thun, MD, Emeritus Vice President of Epidemiological Among her numerous accolades, Dr. Eng has been elected to the American Society
Research at the American Cancer Society, also received a 2018 for Clinical Investigation, the Association of American Physicians and the National
Medal of Honor. Academy of Medicine. She served on the U.S. Department of Health and Human
Services Secretary’s Advisory Committee on Genetics, Health and Society, and has
“Our Medal of Honor recipients embody what the American
been named one of the most influential biomedical researchers in the world.
Cancer Society is all about,” says Gary M. Reedy, Chief
Executive Officer of the American Cancer Society. “We bestow
this highest honor on these individuals for their significant
contributions to the advancement and impact of our collective
efforts to save more lives from cancer.” “We currently can predict a group’s risk of getting specific
Connecting genetic mutations to cancer cancers, but my long-term goal is to predict individuals’ risk,”
says Dr. Eng. “We are looking at various modifying factors that
Dr. Eng has dedicated her career to understanding the genes
interact with germline mutations. The time is ripe to identify
that play a role in heritable cancers and translating those
and deliver targeted therapies for patients with heritable gene
findings into improved patient care.
mutations.”
Her research revealed the relationship between certain germline
Most recently, Dr. Eng’s work has focused on exploring the
PTEN mutations and Cowden syndrome, which carries high
microbiome of cancers, which could offer a new perspective in
risks of breast, thyroid and other cancers. Since then, she and
the battle against the disease.
her colleagues have linked other gene mutations for Cowden
and Cowden-like syndromes as well as pheochromocytoma. “My hope is to find a biomarker that would help us diagnose
These discoveries are helpful for examining the pathogenesis of breast cancer early and easily,” she says. “In our wildest dreams,
common cancers, as well as for diagnosis, prognosis, therapy we hope we can use microbiomics right before breast cancer
and prevention — building the foundation of precision oncology. forms, and then prevent cancer with probiotics or antibiotics.”
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Feb. 13, 2019
Cancer Clinical Trials
Breast Cancer Update: Review of Breast Cancer Symposia
Embassy Suites Hotel Database
Independence, OH
ccfcme.org/breastcancerupdate
Feb. 22-24, 2019 Stay up to date on Cleveland Clinic’s
12th Annual International Symposium on Stereotactic Body Radiation
Therapy and Stereotactic Radiosurgery more than 200 active clinical trials
Grand Floridian Hotel
Orlando, FL for cancer patients.
Visit ccfcme.org as registration information becomes available.
March 8-9, 2019 Search a database of open clinical
2019 Multidisciplinary Head and Neck Cancer Update
Marriott Harbor Beach Resort & Spa trials by disease, phase, physician or
Fort Lauderdale, FL location.
ccfcme.org/headandneck19
April 1-5, 2019; May 13-17, 2019; June 24-28, 2019;
Aug. 19-23, 2019; Oct. 7-11, 2019; Dec. 2-6, 2019 Browse real-time information on each
Leksell Gamma Knife® PerfexionTM Course trial’s objective, eligibility criteria,
Cleveland Clinic Gamma Knife Center
Cleveland, OH phase(s) and more.
Visit ccfcme.org as registration information becomes available.
April 5, 2019 Connect to our Cancer Answer Line
14th Annual Contemporary Issues in Pituitary Disease:
Update on Significant Challenges for more information about a trial or
Cleveland, OH
Visit ccfcme.org as registration information becomes available.
to enroll patients.
Aug. 22-23, 2019
2019 Cleveland Breast Cancer Summit
Cleveland, OH
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To search the database,
Nov. 2-3, 2019
21st Annual Brain Tumor Update and 10th Annual Symposium on Brain go to clevelandclinic.org/
and Spine Metastases Course
Cosmopolitan Hotel
Las Vegas, NV
cancerclinicaltrials
Visit ccfcme.org as registration information becomes available.
TUMOR BOARD SERIES
Complimentary CME-certified webcasts offer expert opinions and discussion
based on case presentations of patients seen at Cleveland Clinic Cancer
Center.
ccfcme.org/tumorboardseries
SPEAKERS BUREAU
Cleveland Clinic Cancer Center Speakers Bureau offers presentations by
leading experts on a full range of oncology topics. Educational sessions are
available to physicians, nurses and other healthcare professionals. Experts
in hematology, medical oncology, radiation oncology, blood and marrow
transplant, palliative medicine, and translational hematology and oncology
research are available. Recent topics have included management of late
effects of cancer treatment, circulating tumor cells and renal cell carcinoma
advancements. To customize a speaker’s program for your organization’s
specific needs or to learn more, contact Sheryl Krall at kralls2@ccf.org or
216.444.7924.
Cleveland Clinic Cancer Center | Care that’s personal. Research that’s revolutionary.T-DM1 + Neratinib’s Safety and
Efficacy in Women with Metastatic
HER2+ Breast Cancer
Phase 1b trial shows good response rate
Despite improvements in surgery, radiation and chemo- Neratinib, on the other hand, targets tumors from within Dr. Abraham is Director
of the Breast Oncology
therapy, 40,000 women still die each year from breast the cell. It is an irreversible tyrosine kinase inhibitor
Program at Cleveland
cancer, many from its most aggressive form, HER2+ (TKI) that interrupts signaling across the ErbB family by Clinic Cancer Center,
breast cancer. inhibiting phosphorylation and activity of HER2, as well Co-Director of the
as epidermal growth factors, HER1 and HER4. Cleveland Clinic
Results of a phase 1b study demonstrate that a new drug Comprehensive Breast
combination offers a promising regimen to attack HER2. Trial characteristics Cancer Program and
Professor of Medicine at
“About 25 percent of breast cancers are HER2+, and they In the trial, patients received concurrent therapy with Cleveland Clinic Lerner
tend to be more aggressive,” says Jame Abraham, MD, T-DM1 (3.6 mg/kg IV) on day 1 of a 21-day cycle and College of Medicine.
Director of the Breast Oncology Program at Cleveland neratinib as a continuous daily oral dose. The neratinib He can be reached at
abrahaj5@ccf.org or
Clinic Cancer Center. “Fortunately, in the past 10 to 15 dose-escalation included four dose levels — 120 mg, 160
216.445.0150.
years, we have developed several new treatment options mg, 200 mg and 240 mg — and used a 3+3 design.
On Twitter:
for HER2+ breast cancer that specifically target the Twenty-four patients were evaluable for toxicity, and @jamecancerdoc
HER2 protein. One is trastuzumab emtansine, T-DM1. 20 were evaluable for efficacy. Dose-limiting toxicity
Unfortunately, not all patients respond to it.” occurred in six patients during cycle 1. Treatment-
Dr. Abraham is the principal investigator of a multi- related grade 3 toxicities included diarrhea (five
institutional phase 1b clinical trial sponsored by the patients), thrombocytopenia (four patients) and ALT
National Surgical Adjuvant Breast and Bowel Project elevation (one patient).
(NSABP). The trial, called NSABP FB-10, combines The response lasted from 42 days to 600-plus days.
T-DM1 and neratinib to treat women with metastatic There was not a correlation of dose and peak or steady-
HER2+ breast cancer who relapsed or progressed after state levels; responses were seen at all doses.
trastuzumab- and pertuzumab-containing regimens.
High response rate
Dr. Abraham presented data from the trial at the 2018
American Society of Clinical Oncology annual meeting. Overall, Dr. Abraham says, the combination of full-dose
T-DM1 and neratinib at 160 mg/d was well-tolerated.
“Neratinib was recently approved for treatment in early The overall response rate was 64 percent, with four
HER2+ breast cancer but not metastatic breast cancer,” patients experiencing a complete response and nine
he says. “This particular trial is testing this drug in experiencing a partial response.
combination with T-DM1 in women who have HER2+
metastatic breast cancer.” “That’s actually pretty high, and we’re really happy with
that,” he says. “We have some patients going on almost
T-DM1 is a conjugated antibody that targets the extra- two years on this regimen.”
cellular domain of HER2. With T-DM1, trastuzumab is
armed to deliver the potent cytotoxic payload of DM1, A phase 2 trial to further test the safety and effectiveness
a maytansinoid antimicrotubule agent, selectively to of the drug combination has already started. Depending
antigen-expressing HER2+ cells. on the results, Dr. Abraham says, a phase 3 trial may
compare patients treated with T-DM1 versus those
treated with T-DM1 and neratinib.
12 | 13 | clevelandclinic.org/cancerCANCER ADVANCES WINTER 2019
The Khorana Score,
10 Years Later
Since its introduction in 2008, the Khorana score has helped clinicians
worldwide calculate the risk of venous thromboembolism (VTE) for
individual cancer patients.
Dr. Khorana is Vice The Khorana score uses readily available clinical infor- updates to avoid adding unnecessary complexity. They
Chair for Clinical
mation like the type of cancer, the complete blood count address this balancing act between precision and
Services and Director
of the Gastrointestinal and a person’s body mass index. Part of its advantage practicality in an editorial published in The Lancet
Malignancies Program at lies in its ease of use. Haematology.1
Cleveland Clinic Cancer
Center. He is also Professor Since Alok Khorana, MD, Vice Chair for Clinical Services The team also wants to ensure that any update provides
of Medicine at Cleveland at Cleveland Clinic Cancer Center, and colleagues a very high positive predictive value — 70 percent or
Clinic Lerner College of
introduced this tool a decade ago, it has been validated greater.
Medicine.
multiple times in different countries and incorporated
He can be reached at Simplicity versus complexity
khorana@ccf.org or into a number of society guidelines. “At Cleveland
216.636.2690. For example, in the same issue of The Lancet
Clinic, we’ve incorporated the score into the electronic
On Twitter: @aakonc Haematology, a new VTE prediction model is pro-
medical record for early detection of potential clots,”
posed based on two factors: tumor site risk (low or
says Dr. Khorana.
intermediate versus high or very high) and D-dimer
Though subsequent investigators dubbed it the concentrations.2
Khorana score, Dr. Khorana credits its utility and
D-dimer assays are widely used in hospitals for other
longevity to the team of colleagues that helped develop
indications. “The test itself is not hard to order, and
this risk stratification and prediction tool, including
you can get results very quickly,” says Dr. Khorana.
Charles W. Francis, MD; Gary H. Lyman, MD, MPH;
“However, D-dimers need to be ordered in most
Nicole M. Kuderer, MD; and Eva Culakova, PhD.
cases — it is not a test routinely done for people with
Updating the score cancer. So it’s an extra step, which can be a challenge
“Despite the score’s persistent relevance over the past because you’re asking oncologists to add more to their
decade,” says Dr. Khorana, “it is time to find new bio- workflow.”
markers to refine the score and increase its accuracy.”
This raises a question: If the new tool is more accurate,
Part of the tool’s popularity is its simplicity, so Dr. is it going to be more widely used? Dr. Khorana and the
Khorana and his team are proceeding carefully with team seek to strike a careful balance between clinical
applicability and improved prediction.
References Over the past decade, some investigators have suggested
1. Khorana AA. Simplicity versus complexity: an existential dilemma as risk tools evolve. adapting the Khorana score to specific cancer types.
Lancet Haematol. 2018;5(7):e273-e274. However, the score is only designed to look at a general
2. Pabinger I, van Es N, Heinze G, et al. A clinical prediction model for cancer-associated cancer population. “We could certainly develop a better
venous thromboembolism: a development and validation study in two independent score for each type of cancer, but we could end up with
prospective cohorts. Lancet Haematol. 2018;5(7):e289-e298. 25 different scores that no one uses,” says Dr. Khorana.
3. Khorana AA, Francis CW. Risk prediction of cancer-associated thrombosis: Appraising
the first decade and developing the future. Thromb Res. 2018;164(Suppl 1):S70-S76.
Cleveland Clinic Cancer Center | Care that’s personal. Research that’s revolutionary.CLEVELAND CLINIC CANCER CENTER | CANCER ADVANCES
Multiple applications over time Future studies
In a report in the journal Thrombosis Research, Dr. Dr. Khorana and the team are currently studying
Khorana reviews more details of how clinicians and whether the Khorana score can be used to identify
researchers have used the Khorana score over the past patients who might benefit from prophylaxis. Dr.
decade.3 Initially, research was focused on discover- Khorana is co-leading a trial with approximately 800
ing risk factors for VTE in people receiving outpatient patients worldwide, assigning patients with a higher
chemotherapy. This research led to an appreciation risk score to prophylaxis with an oral anticoagulant and
that VTE is multifactorial and identifying risk factors is comparing them with a placebo group.
insufficient. Thus, the team developed a risk stratifica-
They also are investigating genomics in lung cancer
tion score.
patients to try to improve risk prediction as well as
Expanded uses for the score have emerged over the evaluating circulating small RNA as a biomarker. Dr.
past decade. Examples include predicting VTE risk in Khorana just received a five-year grant from the National
inpatient cancer settings, designing subsequent throm- Heart, Lung, and Blood Institute to assess these plasma
boprophylaxis studies, targeting education about VTE biomarkers to improve cancer risk prediction. Keith
to high-risk individuals and identifying a subgroup of McCrae, MD, staff in Cleveland Clinic’s Department
cancer patients at risk for early mortality. of Hematology and Medical Oncology, is co-principal
investigator on this grant.
Also in this report, Dr. Khorana addresses the score’s
possible future. A potential adaption of the tool would Not only would identifyng a plasma biomarker for
involve identifying innovative biomarkers that con- cancer be less invasive than taking tumor tissue for a
tribute to precision medicine. “We would also like to biopsy, it could also be easier for monitoring treatment
address the knowledge gap regarding the risk of bleed- response or disease progression over time.
ing in patients treated with thromboprophylaxis, as
The first decade of the Khorana score brought clinicians
well as learn more about how arterial events can lead
an easy-to-use prediction tool to assess their patients’
to stroke and myocardial infarction in a cancer popula-
risk of VTE. With ongoing refinements, conversations
tion,” says Dr. Khorana.
and research, the tool should continue to help clini-
cians help their patients for years to come.
Researchers Receive $4.7M NIH Grant to Prevent Cancer-Associated Thrombosis News
BRIEFS
The National Heart, Lung, and Blood Institute thrombosis is the second-leading cause of death “Cancer-associated blood clots are a critical
(NHLBI), part of the National Institutes of Health, in patients with cancer,” says Dr. Khorana. “This clinical problem, and we urgently need better
awarded a $4.7 million grant to Cleveland Clinic grant will help us address the challenge of ways to predict which patients are at greatest
to study the prevention of life-threatening, cancer- identifying who will develop blood clots and risk,” says Dr. McCrae. “This NHLBI grant will
associated thrombosis. enable us to treat them proactively with blood provide new information that will greatly improve
thinners to prevent this complication.” the management of patients with cancer, arming
The new funding will support a Cleveland
physicians with an advanced statistical tool to
Clinic-led research consortium that will focus on The study will incorporate data from more
better identify who may develop this common and
developing strategies to prevent cancer-associated than 5,000 patients with colorectal, lung and
harmful side effect.”
thrombosis. pancreatic cancer enrolled in clinical trials at
various research centers. Researchers will use The new grant builds on important work initiated
The five-year grant, led by Keith McCrae, MD, and
this robust biobank to identify coagulation-related through Cleveland Clinic’s Center of Excellence
Alok Khorana, MD, supports the creation of a new
and genetic biomarkers associated with abnormal in Cancer Thrombosis Research, which focuses
risk assessment tool to better predict which cancer
blood clotting. They will build on research that on novel approaches to the management and
patients will develop blood clots during treatment.
suggests that activation of a specific blood-clotting prevention of cancer-associated thrombosis.
The project, led by Cleveland Clinic’s Taussig
pathway may contribute to thrombosis, and that Since the center’s establishment in 2016, a
Cancer Institute and Lerner Research Institute, will
biomarkers related to that pathway may identify multidisciplinary team of researchers across
coordinate a consortium of three sites involved in
patients at particularly high risk of blood clots, Cleveland Clinic, with collaborators at Case
this NHLBI program. Other sites are Beth Israel
before they happen. Western Reserve University, have worked to
Deaconess Medical Center (Harvard Medical
study the efficacy of novel therapies, develop
School) and the University of Cincinnati. The team ultimately plans to synthesize these
new preclinical models, and create and expand
data to develop a comprehensive risk calculator
“About 20 percent of cancer patients develop blood biorepositories. Dr. Khorana’s work is supported
by incorporating the identified biomarkers and
clots, which can cause stroke, hospitalization and by the Sondra and Stephen Hardis Chair in
statistical modeling. The online risk assessment
delays in treatment. In fact, cancer-associated Oncology Research.
tool would be available for clinical use.Sarcoma: Rare, Complex, Approachable with Appropriate Care
Dr. Shepard is Co-Director Sarcoma is a rare form of malignancy, accounting Care paths and clinical trials
of the Sarcoma Program
for 1 percent of all adult malignancy diagnoses. An additional Sarcoma Program initiative involves devel-
and Assistant Professor
of Medicine at Cleveland Despite long-standing educational efforts to increase oping specific care paths structured around certain
Clinic Lerner College of recognition and improve practice patterns surrounding bone and soft tissue sarcoma diagnoses. The care paths
Medicine. sarcoma care, the literature shows persistently high reflect the team’s agreement about how best to evaluate
He can be reached at
rates (19 to 60 percent) of unrecognized soft tissue patients, structure timing of multidisciplinary treat-
shepard@ccf.org or
216.445.5670. sarcomas that undergo inappropriate, margin-positive ments and determine frequency and type of disease
On Twitter: @ShepardDale surgical excision. surveillance. Care paths help reduce unnecessary tests
Because of its complexity and rarity, sarcoma requires and decrease time to treatment as well as streamline
a tremendous amount of very specialized expertise and processes in a way that is beneficial to patients and
Dr. Mesko is Co-
Director of the Sarcoma care coordination. Cleveland Clinic’s comprehensive clinicians.
Program, Director of the Sarcoma Program better serves patients by streamlining Definitive care administered at high-volume institutions
Musculoskeletal Tumor
care across multiple disciplines, which enables physi- with a functioning multidisciplinary sarcoma team
Program and Assistant
Professor of Surgery at cians to diagnose and treat patients with great efficiency. leads to lower complication and mortality rates
Cleveland Clinic Lerner
“As soon as a patient is seen in clinic, the medical and better functional outcomes.1 Dr. Shepard and
College of Medicine.
oncology, surgery and radiation oncology teams discuss colleagues see more than 175 newly diagnosed sarcoma
He can be reached at
meskon@ccf.org or the case,” says Dale Shepard, MD, PhD, Co-Director of patients each year. They receive requests for their
216.444.4603.
Cleveland Clinic Cancer Center’s Sarcoma Program. expertise on more than 2,000 pathology consults
On Twitter: @NMeskoMD annually from clinicians across the country.
“We also incorporate psycho-oncology and supportive
care services from the beginning.” “We also offer a wide spectrum of clinical trials, includ-
The Sarcoma Program includes medical oncologists ing surgery, radiation and chemotherapy studies,”
(adult and pediatric), radiation oncologists, orthopaedic says Nathan W. Mesko, MD, orthopaedic surgeon,
surgeons, other surgical subspecialists, pathologists, Co-Director of the Sarcoma Program and Director of the
radiologists, palliative medicine specialists, Musculoskeletal Tumor Program. Examples include
psychosocial oncologists and other practitioners. Each trials led by Lukas Nystrom, MD, Orthopaedic Surgery,
discipline plays a vital role in the care of the sarcoma who is studying wound healing in radiated soft tissue
patient. The multidisciplinary Sarcoma Tumor Board, sarcoma using transcutaneous oxygen; several clinical
which meets weekly, facilitates optimal communication trials from Peter Anderson, MD, Pediatric Hematology
and patient care. All core disciplines are present, submit Oncology and Blood and Marrow Transplantation, who
cases and contribute to the discussion. specializes in pediatric sarcoma; and sarcoma chemo-
therapy trials led by Dr. Shepard, including a trial for a
rare subtype of sarcoma.
Reference
1. Ogura K, Yasunaga H, Horiguchi H, et al. Impact of hospital volume on postoperative complications and in-hospital mortality
after musculoskeletal tumor surgery: analysis of a national administrative database. J Bone Joint Surg Am. 2013;95(18):1684-1691.
Cleveland Clinic Cancer Center | Care that’s personal. Research that’s revolutionary.Left to right: Chirag Shah, MD; Jacob Scott, MD, DPhil; Dale Shepard, MD, PhD: and Nathan W. Mesko, MD
Innovative treatment options for Interstitial brachytherapy is one of the unique Dr. Shah is Director of
Clinical Research and
treatments for retroperitoneal sarcoma offered by
retroperitoneal sarcomas Breast Radiation in the
Drs. Shah and Scott. Very few centers in the U.S. offer Department of Radiation
Two Cleveland Clinic radiation oncologists are this treatment, and Drs. Shah and Scott were recently Oncology and Associate
developing unique treatments for retroperitoneal co-authors on national guidelines regarding this Professor of Medicine at
Cleveland Clinic Lerner
sarcoma, an aggressive disease often presenting close technique. College of Medicine.
to vital tissues. Chirag Shah, MD, and Jacob Scott, MD, He can be reached
External beam radiation therapy. In external beam
DPhil, radiation oncologists and sarcoma specialists, at shahc4@ccf.org or
radiation, a linear accelerator device directs beams of 216.445.8180.
generally target retroperitoneal sarcomas in one of two
high-energy radiation at the tumor from outside the On Twitter: @CShahMD
ways:
body (Figure 1).
Brachytherapy. In this strategy, physicians place one
An advantage of this external delivery is flexibility —
or more catheters in the area surrounding the tumor or Dr. Scott is associate staff
physicians can target the tumor from any angle. Most in the departments of
its resection bed to deliver radiation therapy directly to
people receive a series of treatments, typically five days a Translational Hematology
the sarcoma. Brachytherapy can often deliver a higher and Oncology Research,
week for five to six weeks.
dose of radiation faster and in a more conformal/ and Radiation Oncology.
targeted way as compared with standard external beam (continued on page 18) He can be reached
at scottj10@ccf.org,
radiation. Radioactive implants in these cases are
216.445.5962 or online
temporary. at lerner.ccf.org/thor/
scott/lab.
On Twitter:
@CancerConnector
Figure 1. A 3D surface
representation showing external
beam radiation therapy to treat
retroperitoneal sarcoma.
16 | 17 | clevelandclinic.org/cancer5
CANCER ADVANCES WINTER 2019
Figure 2. Images of radiation treatment plan for retroperitoneal sarcoma sparing normal tissue structures.
(continued) “We also perform image-guided radiation therapy Coordinated care in international guidelines
where we can perform daily tracking of the patient’s To maximize the likelihood of a successful outcome,
tumor with a CT scanner attached to a linear accelera- international guidelines recommend referral of patients
tor during external beam radiation therapy,” Dr. Shah to a high-volume center with a collaborative, multidisci-
says. This helps ensure radiation accurately targets the plinary team of physicians adept at addressing retro-
changing tumor throughout the series of treatments. peritoneal sarcomas.
In conjunction with external beam, Cleveland Clinic The European Society for Medical Oncology (ESMO)
is one of the few centers nationally that offers patients and the European Network for Rare Adult Solid Cancer
an intraoperative radiation therapy boost following (EURACAN), for example, support coordinated, expert
external beam radiation therapy for cases that require care for retroperitoneal sarcomas in new guidelines
additional treatment. released in May 2018.
The importance of precision Advancing care through clinical trials
Retroperitoneal sarcomas often arise very close to Ultimately, each patient and each retroperitoneal
healthy, vital tissue and organs. Dr. Shah and col- sarcoma presentation is unique. “The most important
leagues are evaluating new radiation therapy strategies things to know are that these sarcomas can be quite
for retroperitoneal sarcomas that further refine their aggressive locally, and they can recur,” says Dr. Shah.
ability to minimize risk to nearby organs (Figure 2). In When a physician sees a mass in the retroperitoneum,
so doing, they also hope to minimize some of the side he or she should refer the patient to a high-volume
effects patients experience. For example, they are using sarcoma team right away, he adds.
techniques such as simultaneous integrated boost and
differential dose per fraction that deliver higher doses
to areas away from tissues at risk while rapidly reducing
doses near critical structures.
Cleveland Clinic Cancer Center | Care that’s personal. Research that’s revolutionary.You can also read
