Cancer Consult - Cleveland Clinic · 2013. 12. 20. · CanCER COnsult nOvEmbER 2010 new Program strives to Improve treatment of Elderly Dear Colleagues and Friends: This is an exciting

Ta u s s i g C a n c e r I n s t i t u t e | N o v e m b e r 2 0 10

Cancer Consult

Ranked as one of America’s Top 10 Cancer Programs by U.S.News & World Report.

Clinicians and Researchers Expand Options for Geriatric Cancer Patients

CanCER COnsult nOvEmbER 2010

new Program strives to

Improve treatment of Elderly

Dear Colleagues and Friends:

This is an exciting time for cancer care at Cleveland

Clinic. Previously recognized as the top-ranked cancer

program in Ohio, we have made significant strides in

improving our services, earning a spot in the top 10 in

the country in U.S.News & World Report “America’s Best

Hospitals” survey in 2010. While we are proud of this

acknowledgement, we are not resting on our laurels. We

continue to seek innovative approaches that will improve

outcomes and provide better care for our patients with

cancer.

In this issue of Cancer Consult, I am pleased to share

several of our initiatives aimed at treating the growing

number of older adults with cancer. In 2009, we launched

a new specialty clinic specifically for this vulnerable group of

patients — Taussig Cancer Institute Oncology Program for

Seniors (TOPS). This program focuses on new assessment

tools, models for evaluating specific ethical issues and

techniques for developing new treatment algorithms for

older patients. We are excited about the growth and

success of this program.

We continue to expand our access throughout the region,

working closely with members of our team who are

embedded in Cleveland Clinic regional hospitals and

family health centers, bringing care closer to home for our

patients. In addition, we have developed a specific outreach

program focused on disparities of care and are leading

the nation with creative approaches such as beauty and

barbershop programs, cancer navigation and the evaluation

of training programs.

Cleveland Clinic oncologists and scientists have a robust

basic and clinical research program that continues to earn

international attention. In the pages that follow, you’ll find

several examples of our innovative work, as well as a small

sample of articles authored by cancer program staff so far

this year. We also recently released a new edition of our

Outcomes book, available online, which provides data on

our clinical outcomes and volumes, as well as our patients’

experiences throughout their continuum of care.

I hope you find this edition of Cancer Consult valuable, as it

highlights new directions in our field and offers insight into

our approach to treating cancer. I look forward to continued

collaboration with you.

Sincerely,

Derek Raghavan, MD, PhD, FACP, FRACP

Chairman and Director, Taussig Cancer Institute

M. Frank & Margaret Domiter Rudy Distinguished Chair

ClEvEland ClInIC | taussIG CanCER InstItutE | CanCER COnsult

The Taussig Oncology

Program for Seniors

(TOPS) in Cleveland

Clinic’s Taussig Cancer

Institute addresses the

unique needs of patients

75 years of age and

older who are diagnosed

with cancer.Overcoming Disparities in

Care….3

Geriatric Cancer Care

Research…5

Clinicians and Scientists

Collaborate on Promising

Breast Cancer Research….7

Research Under Way to Clarify

Mechanisms of Cancer-Related

Fatigue….8

Trial Evaluates Combination

Therapy in Myelodysplastic

Syndromes…10

New Brain Metastasis Initiative

Launched……12

Genetic Targets Offer Hope in

Treating Lung Cancer…14

Decision Tree Aids in

Choosing Testicular Cancer

Therapies….16

Prognostic Algorithm to

be Designed for Renal

Cancer…..18

Stimulus Funds Boost Lab

Renovations…..22

Journal Publications….23

(continued on page 2)


New Program Strives

to Improve Treatment

of Elderly

( c o n t i n u e d )

TOPS, launched in July 2009, has a dual goal

of improving clinical care for, and conducting

research specific to elderly patients undergoing

chemotherapy for solid tumors.

TOPS answers the need for the specialized treat-

ment approach these patients require to achieve

the best possible outcomes, says oncologist Dale

Shepard, MD, PhD. He co-directs the geriatric on-

cology program with oncologist Abdo Haddad, MD.

In addition to board certification in oncology,

Dr. Shepard holds a PhD in pharmacology. He

specializes in gastrointestinal and genitourinary

tumors. Dr. Haddad, who is board-certified

in medical oncology, geriatrics and palliative

medicine, specializes in lung and breast tumors.

They form the core of a multidisciplinary team

that includes palliative medicine specialists,

geriatric social workers, pharmacists, physical

therapists, nutritionists, radiation oncologists

and bioethicists.

Every patient in the geriatric oncology program

undergoes a medical and functional assessment

at the first visit that becomes a part of the patient’s

electronic medical record (EMR). This comprehen-

sive assessment for geriatric syndrome includes

evaluation for polyphamacia, nutritional status,

fall risk, mental status and multiple medical

problems. The results of this assessment form

the basis for referrals within the team and to other

Cleveland Clinic specialists, and are essential to

individualized treatment planning for that patient.

Integrating a comprehensive geriatric assessment

like this into cancer treatment for the elderly is a

new approach practiced at only a handful of cancer

centers nationwide, says Dr. Haddad. He believes a

pre-treatment assessment is essential to effectively

treating this population.

“Underlying problems will affect how the patient

will tolerate treatment and must be addressed

prior to treatment to maximize the patient’s

condition. If they are not addressed, problems will

surface after the first cycle of chemotherapy,” he

says. Untreated co-morbidities can contribute to

treatment side effects and are a common cause of

discontinuing treatment in older cancer patients

after a single cycle, he adds.

To manage problems that are identified during the

assessment, patients are referred to a specialist on

the geriatric oncology team or to specialists in the

Cleveland Clinic Center for Geriatric Medicine, if

necessary. The EMR makes patient assessment

results easily accessible to team members and

physicians outside of the Geriatric Oncology

program and facilitates collaborative intervention.

“There tends to be a fear of chemotoxicity in

treating this population simply based on age that

can lead to arbitrary chemotherapy dose reduction

and potentially less than optimal results” he says.

“Age is not a strong predictor of treatment success,

and age alone should not be the criteria for

chemotherapy dose reduction.”

To refer patients to TOPS, call 216.444.7923 or 866.223.8100.


The paucity of data about chemotherapy dosing in

the elderly has motivated Drs. Shepard and Had-

dad to contribute to the body of knowledge in the

field. Defining dosing based on age, functional sta-

tus and co-morbidities has become a primary focus

of the geriatric oncology program’s research. To

this end, all patients are entered into a registry that

captures liver, kidney and cardiac function data

prior to, during and after therapy; tumor response;

and adverse drug effects. The registry eventually

will provide a rich source of data for clinical trials.

Although toxicities or adverse effects occasionally

may require dose reduction when treating elderly

patients, Drs. Shepard and Haddad prefer to

optimize the patient’s condition prior to starting

treatment and then to initiate full dose chemo-

therapy whenever possible in their patients. “Many

patients will benefit from starting with full-dose

therapy,” Dr. Shepard explains.

“Our team has the support and resources to resolve

any problems that may result and adjust the dose

if necessary,” he adds. “Every patient is treated

with curative intent and the goal of prolonging

survival.”

In addition to comprehensive cancer care, TOPS

offers functional assessment and consultation

services to referring physicians for patients over 75

years of age with gastrointestinal, genitourinary,

lung and breast tumors.

“Age is not a strong predictor of

treatment success, and age alone

should not be the criteria for

chemotherapy reduction.”

Overcoming Disparities in Care:

new Programs Offer Improved Outcomes

While Taussig Cancer Institute’s geriatric oncology program is tackling disparities in care for the elderly, several initiatives housed at main campus and at Huron Hospital on Cleveland’s near east side are breaking down barriers in minority populations. The efforts feature vigorous community outreach.

“What we have found is that it’s not enough to edu-cate the community that they need to be screened. The most important mission of community outreach is to build trust in the community so that residents know they can come to us when they have health concerns,” says Kimberly Kreller, RN, BSN, Director of Community Outreach and Research. “We need to bring comprehensive cancer education to them. We have to give them access to necessary screenings, even providing transportation when needed. We can’t start outreach efforts when a patient walks in our door; we have to bring the community to the door.”

In 2009, Angela Bailey, Administrative Program Coordinator for Community Outreach, forged relationships with several local beauty salons and barbershops to provide cancer education and awareness. As part of the program, she trained beauticians and barbers, as well as nail technicians and other staff members, on how to discuss cancer prevention and screening with their clients. The program leverages the warm, trusting environment of a salon to offer cancer information in a non-threatening, natural way to a captive audience. She also equipped each salon with literature including information and the availability of free screenings in

2 | 3 | clevelandclinic.org/cancer



the area such as Mammogram Mondays at Huron Hospital. Ms. Bailey’s outreach efforts are closely tied to Taussig Cancer Institute’s Patient Navigation Program.

With a three-year, $100,000 grant from the Ralph Lauren Cancer Center for Preventative Care — one of five national grantees — the institute has developed the Patient Navigation Program at Huron Hospital, which has a large population of uninsured and under-insured patients. Stacey Booker, RN, MSN, Program Manager for Patient Navigation, has developed a pro-gram that includes a patient navigator. The role of the navigator is to assist any patient in the healthcare sys-tem who has an abnormal finding or cancer diagnosis. The navigator serves as a financial counselor who can help address insurance and other financial issues; and can connect patients with other social service agen-cies as needed. The program models the concept of Patient Navigation founded and pioneered by Harold P. Freeman, MD, in 1990 for the purpose of eliminat-ing barriers to timely cancer screening, diagnosis, treatment and supportive care. This program hopes to see similar success. In its first 10 years, Dr. Freeman’s program changed the five-year survival rate of breast cancer patients from 39 percent to 70 percent.

To further enhance these efforts, Taussig Cancer Institute hosted a one-day symposium in April, “Churches and Hospitals Against Cancer,” in collaboration with the Cleveland Medical Association and the United Pastors in Mission. The event included political, community, and church leaders, along with physicians who discussed barriers to access, diagnosis and management of cancer in minority populations. The group worked together to uncover possible solutions. A task force identified during the event is now creating a cancer tool kit for pastors and community leaders to use to further advance their efforts to eliminate disparities in cancer care. Taussig Cancer Institute will be launching a mobile outreach initiative that will transport residents from churches and other community landmarks to cancer screening locations of their preferences in their geographic areas.

Overcoming Disparities in Care



Anne Lederman Flamm, JD


As a society, we have yet to form

a consensus on the value of cancer

care — what chance of success

and degree of benefit justify the

expenditure of limited resources.

This ethical and philosophical debate plays out

everyday at Cleveland Clinic and other cancer

centers around the country. All cancer patients ask

themselves whether they should choose a treat-

ment that is costly, but could prolong their lives for

an undetermined amount of time. The trade-offs

can be even more challenging for elderly patients

diagnosed with cancer.

Even as the field of geriatric oncology grows, its

goals are not uniformly stated. Some healthcare

professionals assert that treatment of elderly

cancer patients should aim to maintain or aug-

ment quality of life; others emphasize identifying

effective treatments for the geriatric population as

the goal, implying that any divergence from the ap-

proach taken with younger cancer patients reflects

rationing or age-related bias.

Anne Lederman Flamm, JD, Associate Staff in

Cleveland Clinic’s Department of Bioethics, hopes

to shed new light on this ethical dilemma. She is

proposing a research project that involves inter-

viewing elderly cancer patients about whether and

how their age and the cost of treatment influences

their decision to pursue or reject chemotherapy.

Her aim is to increase the understanding of how

elderly patients think about cost and age, allow-

ing oncologists to feel more comfortable speaking

with them about theses issues. “Oncologists need

to recognize the influence of cost on treatment

decisions,” Ms. Flamm stresses.

Rising Population Group, Rising Cancer Rates

The influences of age and cost considerations

have yet to be thoroughly investigated, but they are

important because geriatric patients tend to be on

fixed incomes, and they have comorbidities con-

currently requiring medical treatment and other

forms of supportive care.

GERIATRIC CANCER CARE:

Researcher Hopes to ascertain the Role of age in Cancer treatment decisions by Older Patients




Ms. Flamm says her urgency to research these is-

sues is based on U.S. Census Bureau projections

that the number of people age 65 and older will

double from 35 million to 70 million by 2030,

comprising about 20 percent of the population.

More than 5 percent of the population will be age

80 and older.

The incidence of cancer diagnosed in the elderly is

also rising, she says.

She acknowledges there are empirical studies

suggesting an age bias against treating geriatric

cancer patients across treatment options

— including surgery, chemotherapy and

radiotherapy — despite evidence they tend to do

as well as pediatric and young adult patients when

stage-appropriate therapies are administered.

“Age itself is not the kicker for whether a patient

will or will not do well,” notes Ms. Flamm, adding

other issues, such as performance status, renal

function or a combination of factors, might be

better predictors of success. “Just knowing a

patient is 75 is proving not to tell you much.”

Yet, there is uncertainty and a lack of best evi-

dence as to how to treat geriatric cancer patients.

Physicians often reduce the standard dosage of

a cancer-fighting drug because they are worried

about greater side effects or greater impact of

known side effects.

Elderly patients are historically underrepresented

in clinical trials compared with pediatric pa-

tients and younger adults. When they are offered

participation, elderly patients don’t decline at

any greater rates than other groups, but they are

not offered the opportunity as much. Is that bias,

uncertainty, or is it legitimated in some way by

outcomes? “We don’t have the empirical piece

definitively answered yet,” Ms. Flamm says. “But

depending on what you read, there are people who

find it to be age bias.”

There is a growing movement among some

geriatric oncologists to focus clinical studies

directly on elderly cancer patients. Another push

is for a more comprehensive geriatric assessment

before designing and recommending treatment

options, though Ms. Flamm points out the

present state of healthcare does not lend itself

to compensate in terms of time and money for

an assessment that can take two hours or longer.

(One of the initiatives of Taussig Oncology

Programs for Seniors is to develop a screening

assessment to indicate whether a patient needs a

full, comprehensive assessment.)

Is it Age Bias?

Ms. Flamm hopes her research illuminates whether

and how geriatric cancer patients factor their age

into the decision-making process; for example,

whether and how often patients conclude, “I would

choose this treatment if I was 70, but not at 90,” —

and if so, what is their reasoning. Is it because they

are satisfied with having lived a full life, they don’t

want to experience treatment hardships for what

they see is a limited payoff, or other considerations?

Is that attitude age bias? To the most objective and

dispassionate person, the answer is yes. But is it

age bias if the patient makes the decision for him

or herself?

These questions have implications not just for

individual patient encounters, but for societal

policy as well. Few find age-based limitations a

comfortable proposition to redress rising cancer

care costs. “Should we weigh decisions in geriatric

vs. non-geriatric settings differently?” Ms. Flamm

says. “I would say we could avoid it by being just

as explicit and comprehensive in weighing the

benefits and costs of cancer treatments at every

stage of life.”

Geriatric Cancer Care



For more than 30 years, the search for an effec-

tive breast cancer vaccine has eluded scientists

throughout the world. However, a Cleveland Clinic

researcher recently reported the development of

a vaccine that provides safe and effective protec-

tion against the growth of breast tumors in mouse

models. Remarkably, this protection occurs in the

complete absence of any detectable side effects.

Scientists in the laboratory of Vincent Tuohy, PhD,

Department of Immunology in the Lerner Research

Institute, evaluated a-lactalbumin, a breast specific

protein over-expressed in the majority of human

breast tumors but expressed only during lactation

in the normal breast.

The research involved vaccination of mice with

recombinant mouse a-lactalbumin. The team then

assessed responses in normal mice and in several

mouse breast tumor models, including autochtho-

nous tumors in MMTV-neu and MMTV-PyVT trans-

genic mice, as well as transplantable 4T1 tumors in

BALB/c mice. The data show a significant treat-

ment effect when mice with established breast

tumors are vaccinated and also show a highly

significant inhibition of tumor growth when vac-

cination occurs prior to the appearance of palpable

autochthonous tumors and prior to inoculation of

4T1 breast tumors.

“We are hopeful that this vaccine strategy will

someday be used to prevent breast cancer in adult

women in the same way that vaccines prevent polio

and measles in children,” Dr. Tuohy says.

Derek Raghavan, MD, PhD, Chairman of Taussig

Cancer Institute, expressed cautious optimism

over Dr. Tuohy’s findings.

“This work is intriguing and the science is impres-

sive,” says Dr. Raghavan. “If Dr. Tuohy’s early

research is validated in clinical studies, it could

potentially reduce the incidence of breast cancer.

We’re currently designing trials here at Cleveland

Clinic to test the vaccine in humans, but we’re

five to 10 years way from being able to offer it to

women.”

Financial support is now needed to continue the

processes involved in moving this from the lab to

the research venue to the patient.

Dr. Tuohy’s research is published in Nature

Medicine, June 2010, “A prophylactic, auto-

immune-mediated vaccination strategy for breast

cancer,” and can be found at www.nature.com/

nm/index.html.

Clinicians and scientists Collaborate on Promising breast Cancer Research

“If Dr. Tuohy’s early research is validated in

clinical studies, it could potentially reduce the

incidence of breast cancer.”



“Cancer-related fatigue is complex because it

encompasses a variety of symptoms that develop

over time,” says Mellar Davis, MD, Solid Tumor

Oncology. “Yet, while fatigue is one of the most

common unrelieved symptoms reported by

patients, it is probably the least studied and most

neglected.”

Current interventions, including growth factors,

steroids and hemoglobin each have a niche in

treating cancer-related fatigue. But nothing has

been found to be universally effective.

Dr. Davis is engaged in research designed to corre-

late objective neuromuscular physiologic changes

with fatigue. His team screened 29 advanced

cancer patients and 16 healthy controls to clarify

whether cancer-related fatigue was predominantly

a centrally or peripherally mediated disorder.

Neuromuscular testing of the group involved a

sustained submaximal elbow flexion contraction

at 30 percent maximal level. Endurance time was

measured from the beginning of flexion until the

individual could no longer maintain the flexion.

Both evoked twitch force (a measure of muscle

fatigue) and compound action potential (an

assessment of neuromuscular-junction trans-

mission) were performed during the submaximal

elbow flexion.

“What we found is that when patients with cancer

can no longer continue a task, such as a sustained

contraction, their ability to activate is significantly

reduced relative to normal controls,” says Dr.

Davis. “We noted changes in alpha, gamma and

beta waves that occur, with a delay of recovery of

the EEG signals after a task. There was a distinct

difference between the participants in that cancer-

To learn more about this research or to refer a patient to Dr. Davis, call 216.445.4622 or email [email protected].

Research under Way to Clarify mechanisms of Cancer Related Fatigue

Cancer patients consistently report fatigue as the predominant factor affecting quality of life during

and after treatment. But clinicians struggle to objectify fatigue. Advances in the management of

cancer-related fatigue require better understanding of its underlying mechanisms.


related fatigue patients didn’t recover to normal

patterns as quickly as the control group. There also

is a loss of EEG/EMG coherence as fatigue occurs,

and it was distinctly different in patients with

cancer-related fatigue as compared to controls.”

Together, the findings suggest that central fatigue

plays a more prominent role in cancer-related

fatigue than in normal individuals in tasks that

require endurance.

Case Study Tests Objective Measures

Dr. Davis says that several cohort and phase two

studies have demonstrated that methylphenidate

improves fatigue and cognitive function while

decreasing pain and depression in cancer patients.

He and his colleagues combined objective and

subjective outcomes in a single case study of meth-

ylphenidate in a female patient with severe cancer-

related fatigue. They found that improvements in

her Brief Fatigue Inventory score were associated

with normalization of her neurophysiologic tests.

These results give impetus to understanding the

correlation of physiology with subjective responses

to methylphenidate in the treatment of cancer-

related fatigue and may give clinicians an objective

methodology to study other cancer-related fatigue

interventions.

“We are continuing to analyze our data,” says

Dr. Davis. “If we can isolate the mechanisms

involved in cancer-related fatigue, we may be able

to successfully intervene. Certainly, new drug

development can be based on these mechanisms.”

Charis Eng, MD, PhD, Chair and Founding Director of Cleveland Clinic’s Genomic Medicine Institute, earned the American Cancer Society’s coveted Clinical Research Professor Award. Offered annually to a limited number of established investigators, the award recognizes those who have changed the direction of health policy or clinical, psychosocial, behavioral, or epidemiologic cancer research.

Dr. Eng’s professorship project focuses on PTEN Hamartoma Tumor Syndrome (PHTS) – which confers increased cancer risk – to impact personalized healthcare; facilitate clinical diagnosis, screening, treatment and prevention by increasing the ability to accurately diagnose inheritable cancers; predictively test family members; and assess and manage cancer risk.

Dr. Eng received her undergraduate and medical degrees at the University of Chicago. She completed her residency in Internal Medicine at Beth Israel Deaconess Medical Center in Boston.

Dr. Eng has published more than 260 peer-reviewed original papers in some of the world’s most prominent journals. She has received numerous awards and honors including election to the American Society for Clinical Investigation, to the Association of American Physicians, and as Fellow of the American Association for the Advancement of Science. She received the Doris Duke Distinguished Clinical Scientist Award. Dr. Eng was the recipient of the American Cancer Society’s 2006 John Peter Minton, MD, PhD, Hero of Hope Research Medal of Honor. Recently, she was appointed to the US Department of Health and Human Services Secretary’s Advisory Committee on Genetics, Health, and Society.

Genomic Institute Chair Earns National Award



To refer a patient to Dr. Sekeres, call 216.444.5385 or email [email protected].

Myelodysplastic syndromes (MDS) are a hetero-

geneous group of progressive bone marrow

neoplastic disorders associated with increased

risk for transformation to acute myeloid leukemia

(AML). MDS symptoms include peripheral blood

cytopenias (especially anemia) and dysplastic

changes in one or more hematopoietic lineages.

MDS primarily develops in older adults, with the

median age of diagnosis 71 years.

MDS is a diagnosis that has only been tracked

since 2001. The age-adjusted annual incidence

rate is 3.4 per 100,000 people, which translates

to 10,000 to 15,000 new cases annually and an

estimated 30,000 to 60,000 Americans living with

this disease.

MDS can be primary or secondary (resulting from

cancer treatment with radiation or chemotherapy)

and is divided into two categories: lower-risk

disease, which has a low risk of transformation

to AML and a median survival range of three to

seven years; and higher-risk disease, which has

a pathobiology similar to AML. Patients with

higher-risk MDS either develop AML or die from

complications of the disease, on average within

1.5 years. Approximately 25 percent of newly

diagnosed patients and 15 percent to 20 percent of

established patients have higher-risk disease.

The wide variation in the clinical presentation

of MDS has frustrated treatment strategies and

hindered the development of new therapies.

Stem cell transplant is the only cure for MDS, but

the majority of patients are not eligible due to

older age and other medical problems. In recent

years, three drugs — azacitidine, decitabine and

lenalidomide — have been approved by the U.S.

Food and Drug Administration for the treatment of

MDS or one of its subtypes.

Azacitidine and decitabine, which work through

DNA methyltrasferase inhibition and direct

cytotoxicity, are effective in 40 to 50 percent

of higher-risk patients. The mechanism of

action of lenalidomide has not been definitively

determined, says Cleveland Clinic Leukemia

Program Director Mikkael Sekeres, MD, MS, but

it purportedly works by blocking the effect of

cytokines that cause premature death of cells in

bone marrow and by direct cytotoxic action on the

5q deletion cytogenetic abnormality found in some

patients. Lenalidomide is commonly used to treat

lower-risk MDS.

trial Evaluates Combination therapy in myelodysplastic syndromes Patients

The results of the first Phase I trial combining two FDA-approved drugs

for myelodysplastic syndromes offers new promise for treating higher-risk

patients with this newly recognized and intractable blood marrow disorder.


Combination therapy with azacitidine and lenalid-

omide was chosen for Cleveland Clinic’s Phase

I trial of higher-risk MDS patients based on the

“assumption that the cells in higher-risk disease

retain qualities of lower-risk disease in the bone

marrow microenvironment,” says Dr. Sekeres.

Thus, the complementary mechanisms of the two

agents might yield additive benefit. The goals of

the study were to investigate the safety, tolerance

and response rates of combination therapy.

The multicenter, single-arm, open-label study

evaluated 18 higher-risk patients with a median

age of 68 and a median interval from diagnosis

of five weeks. Their International Prognostic

Scoring System (IPSS) classifications were: Int-1 (2

patients), Int-2 (10 patients) and High (6 patients).

Patients were grouped into four dosing cohorts

and received up to seven cycles of therapy, each

lasting 28 days, and were followed for seven

months. Reported side effects included hemor-

rhage and neutropenic fever. Myelosuppresson,

which was a concern in combining the two drugs,

was not a major side effect.

The overall response rate was 67 percent: eight

patients (44 percent) had a complete response

(CR); three (17 percent) hematologic improve-

ment; and one (6 percent) a marrow CR. Patients

who achieved CR were more likely to have normal

cytogenetics and lower methylation levels. No

dose-limiting toxicities occurred and a maximum

tolerated dose was not reached.

The CR rate was higher than that reported in other

MDS studies. “We were concerned that the two

drugs wouldn’t be more effective together than

they are alone. We were pleasantly surprised by

the results. This finding is a major advance in the

treatment of MDS,” says Dr. Sekeres.

The Phase II trial is currently under way using

the dose (azacitidine: 75/mgm2 daily for 5 days

and lenalidomide: 10mg daily for 21 days) that

achieved the highest rate of CR without any serious

non-hematologic adverse events. The trial will

address the duration of combination therapy and

whether this regimen would be more tolerable

with better efficacy if administered sequentially,

and whether it is best suited to higher-risk patients

with the 5q (del) cytogenetic abnormality.

“The goals of the study were

to investigate the safety,

tolerance and response rates

of combination therapy.”

Clinical trialsDirectory Now Online

Cleveland Clinic Taussig Cancer Institute offers an

online tool for physicians, patients and caregivers to

search for open clinical trials. The web-based clinical

trials database lists all of the trials being managed by

oncologists in the Taussig Cancer Institute that are

accepting patients. At any given time, several hundred

cancer clinical trials are under way on the man campus,

and at some Cleveland Clinic regional facilities.

To search the database, visit

clevelandclinic.org /cancerclinicaltrials



“For many years, oncologists considered brain

metastasis as a uniformly fatal condition, and

treatments were limited to palliative brain

radiation,” says Gene Barnett, MD, Director of

the Brain Tumor and Neuro-Oncology Center at

Cleveland Clinic’s Neurological Institute. “Over

the last two decades, however, approaches that are

more aggressive and accurate have been developed

that may lead to a local cure or a sustained control

of the disease in some patients.”

Nevertheless, Dr. Barnett believes cancer patients

with systemic cancers are poorly informed about

the risks of developing brain metastasis, its early

warning signs and modern therapeutic options

available beyond the traditional treatment of

whole brain radiation.

“Moreover, we have found there are some physi-

cians who may not be mindful of new treatment

options, or may still be of the mindset that brain

metastasis is a uniformly fatal turn in patients

with systemic cancers,” Dr. Barnett observes.

B-Aware program launches

To address this issue, the Brain Tumor and Neuro-

Oncology Center has launched the B-AwareSM

program to educate and empower patients with

information on the risks, symptoms and treat-

ment options that may increase their life-spans

and improve quality of life.

“At the same time, we are actively engaged in

developing physician awareness,” says Dr. Barnett.

“To that end, we officially announced the B-Aware

initiative before physicians who attended the

International Symposium on Long-Term Control

of Secondary Central Nervous System Malignancies

held last spring in Cleveland.”

The Brain Tumor and Neuro-Oncology Center is

collaborating with the American Cancer Society to

promote the B-Aware program on its website.

“The B-Aware program is unique because it is

believed to be the first initiative of its kind to

directly educate cancer patients about the health

issues of brain metastasis,” Dr. Barnett says.

Understanding the symptoms

In addition to the risks, cancer patients also

should know about the common symptoms that

may indicate brain metastasis. Many of the symp-

toms are similar to those of an acute stroke. How-

ever, the symptoms for brain metastasis typically

manifest gradually as opposed to suddenly during

a stroke. Common symptoms include problems

with vision, numbness, weakness, difficulty with

balance, speaking or memory problems, head-

aches that are generally progressive and seizures.

“When patients experience the onset of any of

these symptoms, particularly when the symptoms

begin to become more frequent, prolonged or

become worse, they should see their oncologist im-

mediately,” Dr. Barnett says. “Aggressive therapies

may improve outcomes when brain metastasis is

diagnosed in its early stages.”

At Cleveland Clinic, a multidisciplinary team of

physicians evaluates each patient and recom-

mends an individualized course of treatment that

is most likely to produce an optimal outcome.

“Traditional treatments such as whole brain

radiation and glucocorticoids still play important

roles in the treatment of brain metastasis,” says

Dr. Barnett. “However, for many patients, whole

brain radiation is inadequate to achieve sustained

control and quality. In fact, it may be best reserved

B-Aware PROGRAM:

brain tumor and neuro-Oncology Center launches new brain metastasis Initiative

An estimated 140,000 to 170,000 patients with common systemic cancers are

diagnosed with brain metastasis every year in the United States, particularly patients

with breast, lung and kidney cancers, and melanoma.


for later use as opposed to being used as a first line

of treatment in some cases.”

Aggressive treatments work

Alternatively, research has shown that aggressive

treatments such as minimal access surgery and

radiosurgery can help an appreciable number of

patients to survive up to five years, and in some

cases, up to 10 years.

At the Brain Tumor and Neuro-Oncology Center,

for example, neurosurgeons commonly utilize

aggressive therapies such as minimal access

procedures to extract metastatic tumors. For

patients with new or recurrent metastatic tumors

following radiotherapy, surgery in conjunction

with the placement of carmustine wafers in the

tumor cavity or radiosurgery to the tumor cavity

may preclude local recurrence.

In addition, the Brain Tumor and Neuro-Oncology

Center’s Gamma Knife uses state-of-the-art ste-

reotactic radiosurgery to treat metastatic tumors.

Lesions are typically small (


Over the past several years, research has focused

on uncovering biomarkers, specifically genetic

mutations in lung tumors themselves, which

could lead to targeted treatment. Investigational

treatments focused on two such mutations, the

epidermal growth factor receptor (EGRF) and the

fusion gene echinoderm microtubule associated

protein like 4 – anaplastic lymphoma kinase

(EML4-ALK), are showing promising results.

The population of patients who harbor EGFR

mutations is distinct from those who test positive

for the EML4–ALK fusion gene. Therefore, treat-

ments must be optimized for the individual patient

based on unique characteristics of each cancer,

targeting the specific tumor’s vulnerability.

Cleveland Clinic oncologists are participating in a

Phase III trial of a newly developed ALK inhibitor,

crizotinib, which has demonstrated impressive

activity in an earlier small trial. The degree of

activity was strong, including tumor shrinkage in

90 percent of patients and a 72 percent probability

of remaining progression-free at six months.

Although EML4-ALK- positive tumors represent

only about 5 percent of NSCLC, this translates

into about 10,000 patients annually in the United

States.

These findings come on the heels of FDA-approval

of erlotinib (Tarveca®), an oral small molecule

inhibitor of EGRF, for patients with advanced or

metastatic NSCLC who have failed first- or second-

line chemotherapy. When the mutation is pres-

ent, 70 percent or more of patients will respond

to erlotinib, and the average survival rate tends to

be twice as long as in patients without the EGFR

mutations.

“Given the effectiveness of erlotinib in advanced

NSCLC patient with the EGFR mutation, it makes

sense to investigate the drug in the adjuvant set-

ting,” says Nathan Pennell, MD, PhD, Solid Tumor

Oncology. “We are participating in a phase II trial

of erlotinib in stage I – IIIA patients with the muta-

tion. Patients can still receive standard adjuvant

chemotherapy after surgery prior to starting

erlotinib, and are eligible for enrollment if they

are within six months of surgery.” The goal of the

study is to show an improvement in the number of

patients who are alive and free of recurrence two

years after surgery.

“This work demonstrates a need for tumor tissue

typing in all NSCLCs for drug selection,” says Dr.

Pennell. “It also is exciting because it shows that

once we isolate the molecular mechanisms of a

cancer type, it is possible to quickly develop effec-

tive targeted therapy.”

Both EGFR and EML4-ALK are detected more

frequently in NSCLC patients who were never,

or light (


Patients with clinical stage 1 nonseminomatous

germ cell testicular cancer (CS1 NSGCT) and

their doctors must weigh three primary options

(surgery, chemotherapy and surveillance) and the

potential consequences of those options when

making therapeutic decisions. The complexity

of this challenge is amplified by the absence of

level-one evidence that would identify an option

with maximum survival benefits and minimal side

effects.

For instance, patients unfamiliar with the rigors

and consequences of chemotherapy can find it

difficult to properly imagine and balance the

potential of extended life against the possibility of

late toxicity, secondary malignant neoplasms and

cardiovascular disease that may not appear for

decades.

Investigators at Cleveland Clinic’s Taussig Cancer

Institute and Glickman Urological & Kidney

Institute, Department of Quantitative Health

Science, have created and evaluated a decision

model for CS1 NSGCT that for the first time

offers reasonable estimates of quality adjusted

survival (QAS) for each of the disease’s three initial

therapies — retroperitoneal lymph node dissection

(RPLND), primary chemotherapy and surveillance.

The model is believed to be the first that weighs

both quantity and quality of life. It is designed to

offer physicians a means of formulating a course of

therapy for individual patients and offer patients a

mechanism that allows them to evaluate therapies

in terms of survival and side effects. Although the

patient, with the help of the physician, must still

choose a therapeutic option, the model puts that

decision on a much sounder clinical foundation.

Each of the three initial therapies — surveillance,

RPLND and chemotherapy — is associated with

excellent long-term survival probabilities and

acceptable short- and long-term adverse effects.

Because the outcomes are similar, treatment rec-

ommendations and subsequent patient decisions

have historically been based on physician bias. The

decision tree created by our team offers patients

a grasp of the probabilities of specific clinical

events, the opportunity to see both the decisions

they may have to consider in the future and the

long-term potential outcomes associated with each

of the three initial therapies.

To create the decision tree, the investigators

developed a model that incorporates literature-

derived estimates of survival, treatment-related

morbidity, and patient utilities for each of the

health states that might be a consequence of each

of the three initial treatments. Patient utilities

(a measure of an individual’s preference for a

state of health under conditions of uncertainty)

were derived from 24 healthy volunteers with no

history of cancer. The utilities incorporated in

the model included living with untreated cancer,

To refer a patient to Dr. Gilligan or Dr. Stephenson for evaluation, call 216.444.7923.

decision tree aids in Choosing testicular Cancer therapies

By Timothy Gilligan, MD, and Andrew Stephenson, MD


SurveillanceRPLnd (surgery)Chemotherapy

A

B

SurveillanceRPLnd (surgery)Chemotherapy

45.1

44.1

43.1

42.1

41.1

40.0

39.1

38.1

37.1

Qua

lity-

adju

sted

life

exp

ecta

ncy

0.0 0.1 0.2 0.3 0.4 0.5

Probability of surveillance relapse

0.6 0.7 0.8 0.9 1.0

46.5

45.5

44.5

43.5

42.5

41.5

40.5

39.5

38.5

Qua

lity-

adju

sted

life

exp

ecta

ncy

0.0 0.1 0.2 0.3 0.4 0.5

Probability of surveillance relapse

0.6 0.7 0.8 0.9 1.0

small bowel obstruction, infertility, cardiovascular

disease, second malignant neoplasm, peripheral

neuropathy and ototoxicity. The volunteers were

asked two questions to ascertain their attitudes

toward the conditions in regard to death and their

acceptance of the risk of death versus definitive

treatment.

Noting that the risk of relapse in NSGCT can be

predicted with reasonable confidence using the

histology of the primary tumor and computed

tomography staging, the rating scale analysis

showed that all patients except those at high

risk of relapse, preferred surveillance as the

primary treatment. Active treatment with RPLND

or chemotherapy became the clearly preferred

treatment when the risk of relapse exceeded

46 percent to 54 percent. These findings are

consistent with treatment guidelines that

recommend surveillance for those patients at

low risk for relapse. The QAS differences among

the three treatment options are small, and the

physician and patient, when evaluating the

merits of a therapy, should base decisions on

QAS conditions that are clinically relevant to the

individual patient.

Quality-adjusted life expectancy associated with

retroperitoneal lymph node dissection (RPLND),

primary chemotherapy, and surveillance by the risk

of relapse on surveillance based on utility assess-

ment by a (A) rating scale and (B) standard gamble.



The initial benefit derived from this effort is the

identification of a range of factors found to be

strongly associated with the risk of recurrence

following nephrectomy. Such findings hold the

promise of offering more accurate prognoses, and

as with all studies that identify factors associ-

ated with pathology, they lay the foundation for

a deeper understanding of disease mechanisms

and create avenues for new therapeutic strategies

designed to meet specific risks.

Clear cell renal cell cancer is the most common

form of the highly-aggressive malignancy,

appearing in 3 percent to 4 percent of all new

cancers in the United States, or more than 51,000

cancers annually. It presents two- to three-times

more frequently in men and seems to be more

common in African Americans than Caucasians.

Surgical intervention in early stage disease

(pT1-2) produces very good results with five-year

survival rates ranging from 71 percent to 97

percent following nephrectomy. Despite efforts

to devise post-nephrectomy preventive strategies,

20 percent to 30 percent of these patients will

relapse. Their expected five-year survival is 10

percent. Moreover, the incidence of this disease

has been increasing for the past 50 years.

Identifying factors associated with recurrence

could have a substantial impact on survival.

Genes Associated with

Renal Cancer Recurrence Identified:

Prognostic algorithm to be designed

Cleveland Clinic researchers, in coordination with Genomic Health,

Inc. of Redwood City, Calif, have completed the largest known

genomic study of localized clear cell renal cell carcinoma (cc RCC).

Dr. Rini is a member of the Department of Solid Tumor Oncology. For more information or to refer a patient call 216.444.9567 or email [email protected].

By Brian I. Rini, MD

“Identifying factors associated

with recurrence could have a

substantial impact on survival.”

To identify genes associated with recurrence,

a team of Taussig Cancer Institute researchers

reviewed the records of patients who had

undergone nephrectomy between 1985 and

2003 and selected those for whom paraffin-

embedded tissue samples were available. Patients

with inherited RCC, those who had undergone

neoadjuvant systemic therapy, and those with less

than six months of follow-up were excluded from

the study.

Some 931 patients with complete clinical/

pathological data and tissue samples were

identified. Although Cleveland Clinic is a

tertiary hospital, the demographics of the cohort

paralleled those seen among RCC patients in

the population. The majority (63 percent) of the

patients were male, with a median age of 61. Stage

I disease was dominant, appearing in 68 percent

of the cohort; stage II appeared in 10 percent;

and stage III made up 22 percent. The clinical/

pathological covariates associated with the

patients’ recurrence-free interval (RFI) included

microscopic necrosis, Fuhrman grade, stage,

tumor size and lymph node involvement.

RNA was extracted from 6 x 10 μm tissue sections

and screened for 732 genes, five of which were

used as reference. Researchers identified 300

genes that were significantly associated with four

or more of the five covariates (p


several taussig Cancer Institute physicians were recently awarded “top” rankings from two independent national sources.

Aplastic AnemiaJaroslaw Maciejewski, MD, PhD

Castle Connolly “Top Doctors” Cleveland Magazine Best Doctors

Mikkael Sekeres, MD, MSCastle Connolly “Top Doctors” Cleveland Magazine Best Doctors

Benign HematologyAlan Lichtin, MD


Jaroslaw Maciejewski, MD, PhD


Roy Silverstein, MDCleveland Magazine Best Doctors

Bladder CancerRobert Dreicer, MD


Jorge Garcia, MDCleveland Magazine Best Doctors

Timothy Gilligan, MDCleveland Magazine Best Doctors

Derek Raghavan, MD, PhDCastle Connolly “Top Doctors” Cleveland Magazine Best Doctors

Brian Rini, MDCastle Connolly “Top Doctors” Cleveland Magazine Best Doctors

Bone Marrow TransplantBrian Bolwell, MD


Edward Copelan, MDCastle Connolly “Top Doctors”Cleveland Magazine Best Doctors

Matt Kalaycio, MDCastle Connolly “Top Doctors” Cleveland Magazine Best Doctors

Brad Pohlman, MDCastle Connolly “Top Doctors” Cleveland Magazine Best Doctors

John Sweetenham, MDCastle Connolly “Top Doctors” Cleveland Magazine Best Doctors

Brain Tumor - Adult & PediatricDavid Peereboom, MD


John Suh, MDCastle Connolly “Top Doctors” Cleveland Magazine Best Doctors

Breast CancerG. Thomas Budd, MD


Charis Eng, MDCastle Connolly “Top Doctors” Cleveland Magazine Best Doctors

Roger Macklis, MDCastle Connolly “Top Doctors” Cleveland Magazine Best Doctors

Cancer GeneticsCharis Eng, MD


Esophageal CancerDavid Adelstein, MD


Gregory Videtic, MDCastle Connolly “Top Doctors” Cleveland Magazine Best Doctors

Gastrointestinal TumorsRobert Pelley, MD

Cleveland Magazine Best Doctors

General OncologyOmer Koc, MD

Cleveland Magazine Best DoctorsGary Schnur, MD

Cleveland Magazine Best DoctorsVinit Makkar, MD

Cleveland Magazine Best Doctors

Head & Neck CancerDavid Adelstein, MD


Jerrold Saxton, MDCleveland Magazine Best Doctors

Kidney CancerRobert Dreicer, MD






LeukemiaEdward Copelan, MD


Matt Kalaycio, MDCastle Connolly “Top Doctors” Cleveland Magazine Best Doctors


Lung CancerDavid Adelstein, MD



LymphomaBrian Bolwell, MD


Roger Macklis, MDCastle Connolly “Top Doctors” Cleveland Magazine Best Doctors

Brad Pohlman, MDCastle Connolly “Top Doctors” Cleveland Magazine Best Doctors

John Sweetenham, MDCastle Connolly “Top Doctors” Cleveland Magazine Best Doctors

MelanomaPierre Triozzi, MD

Castle Connolly “Top Doctors”Ernest Borden, MD


Cleveland ClinicTaussig Cancer Institute9500 Euclid Ave./R35Cleveland, OH 44195216.444.7923

Fairview Hospital18101 Lorain Ave.Cleveland, OH 44111216.476.7000

Hillcrest Hospital6780 Mayfield RoadMayfield Heights, OH 44124440.312.4500

Huron Hospital13951 Terrace RoadEast Cleveland, OH 44112Phone: 216-761-4258

BeachwoodFamily Health and Surgery Center26900 Cedar RoadBeachwood, OH 44122216.839.3000 or 800.801.2233

IndependenceCancer Center6100 Westcreek RoadSte. 15 & 16Independence, OH 44131216.524.7979, Medical Oncology216.447.9747, Radiation Oncology

LorainFamily Health and Surgery Center5700 Cooper Foster Park RoadLorain, OH 44053440.204.7400 or 800.272.2676

ParmaCancer Center6525 Powers Blvd.Parma, OH 44129440.743.4747

StrongsvilleFamily Health and Surgery Center16761 SouthPark CenterStrongsville, OH 44136440.878.2500 or 800.239.1098

TwinsburgMedical Offices22365 Edison Blvd., Suite 100Twinsburg, OH 44087330.888.4000

Willoughby HillsFamily Health Center2570 SOM Center RoadWilloughby Hills, OH 44094440.943.2500 or 800.807.2888

WoosterSpecialty Center721 East Milltown RoadWooster, OH 44691330.287.45000 or 800.451.9870

Ca

nC

ER

Ca

RE

lO

Cat

IOn

s


Myelodysplastic SyndromesJaroslaw Maciejewski, MD, PhD



Palliative CareMellar Davis, MD


Declan Walsh, MDCleveland Magazine Best Doctors

Prostate CancerJay Ciezki, MD


Robert Dreicer, MDCastle Connolly “Top Doctors” Cleveland Magazine Best Doctors





Ovarian CancerCharis Eng, MD


Radioimmunotherapy of CancerRoger Macklis, MD


Stereotactic RadiosurgeryJohn Suh, MD



Testicular CancerRobert Dreicer, MD






Taussig Cancer Institute has been awarded more than $2 million from the American Recovery and Reinvest-ment Act (ARRA) for the renovation and expansion of its translational cancer research facilities.

The National Center for Research Resources, part of the National Institutes of Health, awarded the grant, which will create 17 new jobs.

The project involves the renovation of the original 3,600 square feet of laboratory space built on Cleveland Clinic’s main campus in 1928. The historic space was last renovated in the 1950s, and its use has diminished in recent decades due to the availability of new, more state-of-the-art facilities.

The renovation will include modernizing the space to meet current research laboratory standards, creating a shared instrumentation room that will free up an additional 500 square feet to allow for more bench research, and installing major, fixed research equipment. The expanded lab area also will allow for the recruitment of up to four new independent researchers, along with 12 new technical support positions and one administrative assistant position.

“The expansion of our translational cancer research capabilities is essential to the mission of the Taussig Cancer Institute,” says Chairman Derek Raghavan, MD, PhD “This award will allow us to continue to bring the latest research straight from the lab to the bedside to aid in the diagnosis and treatment of patients.”

Currently, 42 scientists and technicians along with six administrative staff members occupy the avail-able laboratory space in the Taussig Cancer Institute, which is at capacity.

stimulus Funds boost Cancer Research lab Renovation


ClEvEland ClInIC | taussIG CanCER InstItutE | PublICatIOns

A Sampling of 2010 Journal Publications

Adelstein DJ, Rodriguez CP. Human papillomavirus: chang-

ing paradigms in oropharyngeal cancer. Curr Oncol Rep.

2010 Mar;12(2):115-120.

Adelstein DJ, Moon J, Hanna E, Giri PGS, Mills GM, Wolf GT,

Urba SG. Docetaxel, cisplatin, and fluorouracil induction

chemotherapy followed by accelerated fractionation/

concomitant boost radiation and concurrent cisplatin in

patients with advanced squamous cell head and neck

cancer: A Southwest Oncology Group phase II trial (S0216).

Head Neck. 2010 Feb;32(2):221-228.

Advani A, Coiffier B, Czuczman MS, Dreyling M, Foran J, Gine

E, Gisselbrecht C, Ketterer N, Nasta S, Rohatiner A,

Schmidt-Wolf IGH, Schuler M, Sierra J, Smith MR, Verhoef

G, Winter JN, Boni J, Vandendries E, Shapiro M, Fayad L.

Safety, pharmacokinetics, and preliminary clinical activity

of inotuzumab ozogamicin, a novel immunoconjugate for

the treatment of B-cell non-Hodgkin’s lymphoma: results

of a phase I study. J Clin Oncol. 2010 Apr 20;28(12):2085-

2093.

Advani AS, Lim K, Gibson S, Shadman M, Jin T, Copelan E,

Kalaycio M, Sekeres MA, Sobecks R, Hsi E. OCT-2 expres-

sion and OCT-2/BOB.1 co-expression predict prognosis in

patients with newly diagnosed acute myeloid leukemia.

Leuk Lymphoma. 2010 Apr;51(4):606-612.

Ahluwalia MS, Gladson CL. Progress on antiangiogenic

therapy for patients with malignant glioma. J Oncol.

2010;2010:689018.

Ballen KK, Shrestha S, Sobocinski KA, Zhang MJ, Bashey A,

Bolwell BJ, Cervantes F, Devine SM, Gale RP, Gupta V, Hahn

TE, Hogan WJ, Kroger N, Litzow MR, Marks DI, Maziarz RT,

McCarthy PL, Schiller G, Schouten HC, Roy V, Wiernik PH,

Horowitz MM, Giralt SA, Arora M. Outcome of transplanta-

tion for myelofibrosis. Biol Blood Marrow Transplant. 2010

Mar;16(3):358-367.

Bauer S, Parry JA, Muhlenberg T, Brown MF, Seneviratne D,

Chatterjee P, Chin A, Rubin BP, Kuan SF, Fletcher JA,

Duensing S, Duensing A. Proapoptotic activity of bortezo-

mib in gastrointestinal stromal tumor cells. Cancer Res.

2010 Jan 1;70(1):150-159.

Bianco FJ, Jr., Vickers AJ, Cronin AM, Klein EA, Eastham JA,

Pontes JE, Scardino PT. Variations among experienced

surgeons in cancer control after open radical prostatec-

tomy. J Urol. 2010 Mar;183(3):977-982.




Chow E, James J, Barsevick A, Hartsell W, Ratcliffe S, Scaran-

tino C, Ivker R, Roach M, Suh J, Petersen I, Konski A, Demas

W, Bruner D. Functional interference clusters in cancer

patients with bone metastases: a secondary analysis of

RTOG 9714. Int J Radiat Oncol Biol Phys. 2010 Apr;76(5):1507-

1511.

Ciezki JP, Reddy CA, Stephenson AJ, Angermeier K, Ulchaker

J, Altman A, Chehade N, Klein EA. The importance of

serum prostate-specific antigen testing frequency in

assessing biochemical and clinical failure after prostate

cancer treatment. Urology. 2010 Feb;75(2):467-471.

Cortes JE, Baccarani M, Guilhot F, Druker BJ, Branford S, Kim

DW, Pane F, Pasquini R, Goldberg SL, Kalaycio M, Moiraghi

B, Rowe JM, Tothova E, De Souza C, Rudoltz M, Yu R,

Krahnke T, Kantarjian HM, Radich JP, Hughes TP. Phase

III, randomized, open-label study of daily imatinib

mesylate 400 mg versus 800 mg in patients with newly diag-

nosed, previously untreated chronic myeloid leukemia in

chronic phase using molecular end points: tyrosine kinase

inhibitor optimization and selectivity study. J Clin Oncol.

2010 Jan 20;28(3):424-430.

Davis MP. Re: Establishing “best practices” for opioid

rotation. J Pain Symptom Manage. 2010 Jan;39(1):e1-e2.

Dean RM, Pohlman B, Sweetenham JW, Sobecks RM,

Kalaycio ME, Smith SD, Copelan EA, Andresen S, Rybicki

LA, Curtis J, Bolwell BJ. Superior survival after replacing

oral with intravenous busulfan in autologous stem cell

transplantation for non-Hodgkin lymphoma with busul-

fan, cyclophosphamide and etoposide. Br J Haematol. 2010

Jan;148(2):226-234.

Descovich M, Fowble B, Bevan A, Schechter N, Park C, Xia P.

Comparison between hybrid direct aperture optimized

intensity-modulated radiotherapy and forward planning

intensity-modulated radiotherapy for whole breast

irradiation. Int J Radiat Oncol Biol Phys. 2010 Jan 1;76(1):91-

99.

Dong B, Silverman RH. Androgen stimulates transcription

and replication of xenotropic murine leukemia virus-relat-

ed virus. J Virol. 2010 Feb;84(3):1648-1651.

Du Y, Fryzek J, Sekeres MA, Taioli E. Smoking and alcohol

intake as risk factors for myelodysplastic syndromes

(MDS). Leuk Res. 2010 Jan;34(1):1-5.

Ebrahem Q, Chaurasia SS, Vasanji A, Qi JH, Klenotic PA,

Cutler A, Asosingh K, Erzurum S, Anand-Apte B. Cross-talk

between vascular endothelial growth factor and matrix

metalloproteinases in the induction of neovascularization

in vivo. Am J Pathol. 2010 Jan;176(1):496-503.

Bishop MR, Dean RM, Steinberg SM, Odom J, Pollack SM,

Pavletic SZ, Sportes C, Gress RE, Fowler DH. Correlation of

pretransplant and early post-transplant response assess-

ment with outcomes after reduced-intensity allogeneic

hematopoietic stem cell transplantation for non-Hodgkin’s

lymphoma. Cancer. 2010 Feb 15;116(4):852-862.

Bennett KL, Romigh T, Eng C. Disruption of transforming

growth factor-beta signaling by five frequently methylated

genes leads to head and neck squamous cell carcinoma

pathogenesis. Cancer Res. 2009 Dec 15;69(24):9301-9305.

Borden EC, Raghavan D. Personalizing medicine for cancer:

the next decade. Nat Rev Drug Discov. 2010 May;9(5):343-

344.

Brimo F, Robinson B, Guo C, Zhou M, Latour M, Epstein JI.

Renal epithelioid angiomyolipoma with atypia: a series of

40 cases with emphasis on clinicopathologic prognostic

indicators of malignancy. Am J Surg Pathol. 2010

May;34(5):715-722.

Brawley OW, Newman LA, Raghavan D. Reply to M. Moore et

el [Patient comorbidities and behaviour once diagnosed

are major contributors to disparities in cancer health

outcomes]. J Clin Oncol. 2010 Jan 20;28(3):e38.

Cai R, Barnett GH, Novak E, Chao ST, Suh JH. Principal risk of

peritumoral edema after stereotactic radiosurgery for

intracranial meningioma is tumor-brain contact interface

area. Neurosurgery. 2010 Mar;66(3):513-522.

Campbell SC, Bhoopalam N, Moritz TE, Pandya M, Iyer P,

Vanveldhuizen P, Ellis NK, Thottapurathu L, Garewal H,

Warren SR, Friedman N, Reda DJ. The use of zoledronic

acid in men receiving androgen deprivation therapy for

prostate cancer with severe osteopenia or osteoporosis.

Urology. 2010 May;75(5):1138-1143.

Campbell SC, Faraday M, Uzzo RG. Small renal mass. N Engl J

Med. 2010 Jun 17;362(24):2334-2335.

Chigurupati S, Venkataraman R, Barrera D, Naganathan A,

Madan M, Paul L, Pattisapu JV, Kyriazis GA, Sugaya K,

Bushnev S, Lathia JD, Rich JN, Chan SL. Receptor channel

TRPC6 is a key mediator of Notch-driven glioblastoma

growth and invasiveness. Cancer Res. 2010 Jan 1;70(1):418-

427.

Chao J, Budd GT, Chu P, Frankel P, Garcia D, Junqueira M,

Loera S, Somlo G, Sato J, Chow WA. Phase II clinical trial of

imatinib mesylate in therapy of KIT and/or PDGFRalpha-

expressing Ewing sarcoma family of tumors and desmo-

plastic small round cell tumors. Anticancer Res. 2010

Feb;30(2):547-552.



Eng C, Sharp RR. Bioethical and clinical dilemmas of

direct-to-consumer personal genomic testing: the problem

of misattributed equivalence. Sci Transl Med. 2010 Feb

3;2(17):17cm5.

Friedberg JW, Sharman J, Sweetenham J, Johnston PB, Vose

JM, Lacasce A, Schaefer-Cutillo J, De Vos S, Sinha R,

Leonard JP, Cripe LD, Gregory SA, Sterba MP, Lowe AM,

Levy R, Shipp MA. Inhibition of Syk with fostamatinib

disodium has significant clinical activity in non-Hodgkin

lymphoma and chronic lymphocytic leukemia. Blood. 2010

Apr 1;115(13):2578-2585.

Gore SD, Gojo I, Sekeres MA, Morris L, Devetten M, Jamieson

K, Redner RL, Arceci R, Owoeye I, Dauses T, Schachter-

Tokarz E, Gallagher RE. Single cycle of arsenic trioxide-

based consolidation chemotherapy spares anthracycline

exposure in the primary management of acute promyelo-

cytic leukemia. J Clin Oncol. 2010 Feb 20;28(6):1047-1053.

Hauser K, Walsh D. How to make palliative care services

financially viable. European Journal of Palliative Care. 2010

Jan-Feb;17(1):36-40.

Huang D, Ding Y, Zhou M, Rini BI, Petillo D, Qian CN,

Kahnoski R, Futreal PA, Furge KA, Teh BT. Interleukin-8

mediates resistance to antiangiogenic agent sunitinib in

renal cell carcinoma. Cancer Res . 2010 Feb 1;70(3):1063-

1071.

Kalaycio ME, Kukreja M, Woolfrey AE, Szer J, Cortes J,

Maziarz RT, Bolwell BJ, Buser A, Copelan E, Gale RP, Gupta

V, Maharaj D, Marks DI, Pavletic SZ, Horowitz MM, Arora

M. Allogeneic hematopoietic cell transplant for prolym-

phocytic leukemia. Biol Blood Marrow Transplant. 2010

Apr;16(4):543-547.

Kantarjian H, Fenaux P, Sekeres MA, Becker PS, Boruchov A,

Bowen D, Hellstrom-Lindberg E, Larson RA, Lyons RM,

Muus P, Shammo J, Siegel R, Hu K, Franklin J, Berger DP.

Safety and efficacy of romiplostim in patients with

lower-risk myelodysplastic syndrome and thrombocytope-

nia. J Clin Oncol. 2010 Jan 20;28(3):437-444.

Kerr BA, Byzova TV. alphaB-crystallin: a novel VEGF chaper-

one. Blood. 2010 Apr 22;115(16):3181-3183.

Koc ON, Redfern C, Wiernik PH, Rosenfelt F, Winter JN,

Carter WD, Gold DP, Stewart ME, Ghalie RG, Bender JF. A

phase 2 trial of immunotherapy with mitumprotimut-T

(Id-KLH) and GM-CSF following rituximab in follicular

B-cell lymphoma. J Immunother. 2010 Feb;33(2):178-184.

Ko JS, Rayman P, Ireland J, Swaidani S, Li G, Bunting KD, Rini

B, Finke JH, Cohen PA. Direct and differential suppression

of myeloid-derived suppressor cell subsets by sunitinib is

compartmentally constrained. Cancer Res. 2010 May

1;70(9):3526-3536.

Koo BH, Coe DM, Dixon LJ, Somerville RPT, Nelson CM,

Wang LW, Young ME, Lindner DJ, Apte SS. ADAMTS9 is a

cell-autonomously acting, anti-angiogenic metalloprotease

expressed by microvascular endothelial cells. Am J Pathol.

2010 Mar;176(3):1494-1504.

Kulkarni S, Reddy KB, Esteva FJ, Moore HCF, Budd GT, Tubbs

RR. Calpain regulates sensitivity to trastuzumab and

survival in HER2-positive breast cancer. Oncogene. 2010

Mar 4;29(9):1339-1350.

Lamborn KR, Vogelbaum MA, van den Bent MJ, Chang SM.

Updated response assessment criteria for high-grade

gliomas: response assessment in neuro-oncology working

group. J Clin Oncol. 2010 Apr 10;28(11):1963-1972.

Lasheen W, Walsh D, Mahmoud F, Sarhill N, Rivera N, Davis

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Cancer Consult Medical EditorBrian Rini, MDSolid Tumor Oncology

Cancer Consult Editorial Board

Derek Raghavan, MD, PhD, Chairman, Taussig Cancer Institute

Brian Bolwell, MD, Chairman,Hematologic Oncology and Blood Disorders

Robert Dreicer, MD, Chairman, Solid Tumor Oncology

Timothy Spiro, MD, Chairman, Regional Oncology

John Suh, MD, Chairman, Radiation Oncology

Gene Barnett, MD, Director, Brain Tumor and Neuro-Oncology Center

Eric Klein, MD, Chairman, Urologic Oncology,Glickman Urological & Kidney Institute

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Cancer Consult - Cleveland Clinic · 2013. 12. 20. · CanCER COnsult nOvEmbER 2010 new Program strives to Improve treatment of Elderly Dear Colleagues and Friends: This is an exciting