Precision Medicine Program
The rapidly evolving field of precision medicine shows great promise in
the treatment, early detection, and risk management of cancer. Cancer
is driven by gene abnormalities – mutations, rearrangements, deletions,
amplifications – that alter cell behavior and cause malignancies.
As the understanding of the cancer genome advances, along with further
development of molecularly targeted drugs, physicians’ ability to
select the most effective treatment for each patient’s tumor based
on its molecular profile is improved. The Precision Medicine Program was
launched at Hoag in 2016, positioning Hoag Family Cancer Institute on
the leading edge of precision medicine clinical implementation and research.
Michael Demeure, M.D., M.B.A., F.A.C.S., F.A.C.E., was recruited to Hoag
in 2017 to lead the Precision Medicine Program. Prior to joining Hoag,
Dr. Demeure led an active research lab for over 20 years, focusing his
efforts on the use of genomic technologies to develop novel biomarkers,
new therapeutic targets, and related therapies in the management of endocrine
and gastrointestinal cancers. Dr. Demeure is joined by molecular pathologist,
David Braxton, M.D., Carole Norman, R.N., precision medicine program manager,
variant scientist and educator, Sourat Darabi, Ph.D., medical geneticist,
Valentina Dalili-Shoaie, M.D., genetic counselors, Jeanne Homer, M.S.,
Frances Oh, M.S., Chelsey Weatherill, M.S., and additional leadership
from Burton Eisenberg, M.D., executive medical director of Hoag Family
Cancer Institute and Grace E. Hoag Executive Medical Director Endowed Chair.
HOAG FAMILY CANCER INSTITUTE’S PRECISION MEDICINE PROGRAM FOCUSES
ON THREE AREAS:
Tumor Profiling
Technology for genetic profiling of cancers has become increasingly sophisticated
while the cost of profiling has decreased dramatically. Hoag Family Cancer
Institute collaborates with Caris Life Sciences and other commercial labs
for profiling and bioinformatic analysis. Our guiding priority is to profile
patients with metastatic disease whose tumors have not responded to standard
therapy to discover opportunities for clinical trials or an alternate
treatment approach. These results are often discussed in disease site
specific tumor boards. A monthly molecular tumor board highlights interesting
and unique patient tumor genomic results.
In certain cancers, notably lung cancer, tumor profiling has become standard
practice before beginning chemotherapy. A patient whose non-small cell
lung cancer has an ALK fusion, for example, will have a better response
to a drug that targets the abnormal ALK protein than they would to chemotherapy
and will experience fewer adverse side effects.
Beginning in 2016, Hoag Family Cancer Institute incorporated tumor profiling
as the standard for patients with advanced cancer within several of the
Institute’s multidisciplinary site-specific cancer programs.
All patients diagnosed with lung cancer (stage 1b or greater) whose biopsies
are performed at Hoag receive tumor profiling through Caris Life Sciences’
Molecular Intelligence® panel of over 600 cancer genes. Caris provides
a detailed report that includes relevant biomarkers, drug response prediction
– both beneficial and non-beneficial, mutation load, clinical trials
for which the patient may be eligible, and level of evidence associated
with each biomarker gene association.
"Hoag's Precision Medicine Program has allowed me to provide treatment
tailored to both the patient and the tumor. DNA is the key to targeted
anti-cancer therapies. The program has given me the knowledge to predict
which treatments will have the highest chance of success and improve my
patients’ outcome.""
-George Semeniuk, M.D.
Medical Oncologist
Hoag patients with lung cancer have had their tumors profiled since the
initiative launched in late 2016. The Head & Neck Cancer Program and
GYN Oncology Program have also incorporated consistent tumor profiling.
A discussion of patients’ results and how it may affect their treatment
course are incorporated in each program’s tumor board meeting.
The Precision Medicine team of experts at Hoag reviews the results of each
patient’s tumor profiling to evaluate the findings and offer additional
insights and guidance to treating oncology physicians. Hoag’s molecular
pathologist, one of only three in the entire Providence Health system,
adds an extra level of expertise to the program. The team stays current
on the ever-changing molecular testing technology, drug-gene associations
and clinical trials with new cancer drugs in order to serve as a resource
to clinicians.
Through Hoag’s partnerships with Caris Life Sciences and Syapse,
a software platform for precision medicine, Hoag can access and contribute
to two robust databases of patient tumor molecular profile results and
targeted treatment outcomes. The information includes data from leading
cancer centers at major academic research facilities across the United
States that are also members of these precision medicine networks.
Collaboration with Hereditary Cancer Program and High-Risk Cancer Programs
While historically there has been a large focus on hereditary cancer screening
for breast and ovarian cancer, recent recognition of other relevant germline
genetic mutations indicating an increased risk for other cancers has led
to an increased role for germline testing. In collaboration with the Precision
Medicine Program, the Hereditary Cancer Program’s testing for cancers
other than breast and ovarian is steadily increasing.
"At Hoag, we work together relentlessly to dissect the inner workings
of cancer cells. As a result of the Precision Medicine Program, we keep
getting closer to more effective treatments with less side effects."
N. Simon Tchekmedyian, M.D.
Medical Oncologist
Hoag’s Precision Medicine team, in an effort lead by our molecular
pathologist, Dr. David Braxton, reviews each Caris report in order to
identify mutations that could be related to germline genetics so that
appropriate patients can be referred to genetic testing through Hoag’s
Hereditary Cancer Program. In nearly half of cases, germline testing reveals
mutations in unsuspected genes not necessarily related to the patient’s
primary cancer. Of course, germline mutation screening is also critical
in the identification of family members who could be at increased risk
for cancer.
Patients and family members identified may be referred to one of Hoag Family
Cancer Institute’s cancer specific high risk or screening programs
for ongoing tumor surveillance, early detection or intervention. They
may also be referred to the program’s board-certified medical geneticist.
Another unique program developed by Hoag’s Precision Medicine and
Hereditary Cancer teams is the initiation of a clinical research study
using whole-body MRI screening for patients who have a germline TP53 mutation,
or Li-Fraumeni Syndrome, identified through genetic testing. Individuals
who carry a germline TP53 mutation are predisposed to many different cancers
including brain tumors, lung cancer, sarcoma, adrenal cancer, leukemia,
and breast cancer. To date, there is no consensus or guidelines on how
these patients should best be monitored. Through this MRI screening study,
the hope is to enable identification of cancers at an early stage when
they are most treatable.
"I applaud Hoag for embracing state-of-the-art precision medicine
for its patients. It has afforded me the opportunity of tailoring diagnoses
to the individual characteristics of each patient and his or her disease.
Hoag patients can now expect not only more accurate diagnoses, but increased
treatment options including clinical trials. Precision medicine allows
me to practice at the forefront of cancer research."
Janet Stallman, M.D.
Pathologist
Resource to Hoag’s Medical Oncology Community
Precision medicine and genomics are advancing rapidly and changing the
landscape of cancer care. While the potential benefit to patients is vast,
the challenge for oncologists lies in making sense of an overwhelming
amount of new information – information they were not likely introduced
to in medical school – and appropriately putting it to use all while
maintaining busy clinical practices. The Precision Medicine Program intends
to partner with Hoag’s medical oncologists in digesting the copious
amounts of new and changing genomic information.
Dr. Demeure, Dr. Darabi and the team participate in tumor boards in order
to present and interpret relevant genomic information, facilitate lectures
and presentations from experts in the field, and are available as a resource
to consult on the selection of appropriate tumor profiling panels, interpretation
of results and the evaluation of treatment options.
INNOVATION AND CLINICAL RESEARCH
The newness of precision medicine approaches warrants demonstration of
clinical utility, which means it is being used by doctors to guide care
and it is helping patients achieve better outcomes. Hoag’s Precision
Medicine Program participates in several multicenter research studies
and initiates its own research studies.
One such pilot research study is in pharmacogenetics. One’s genes
affect how one metabolizes drugs, how effective some drugs may be and
whether the individual may have an increased risk of an adverse reaction
to a drug. The FDA has identified over 100 such drug-gene associations
involving 22 genes. Genetic testing for inherent genetic differences can
pinpoint a patient’s response to various medications. The information
can help doctors select and appropriately dose certain drugs. It is also
hoped that this process can be a major factor in decreasing toxicity and
hospitalization from adverse drug reactions. Hoag’s study will accrue
50 patients whose DNA obtained from oral swabs is sent to a commercial
lab for a 22 gene panel test. Their clinical and pharmacy history is then
analyzed with the genetic results.
Hoag’s study is testing the hypothesis that genetic analysis will
demonstrate at least 30% of patients are currently taking a drug for which
there is a pharmacogenetics cautionary variant. Secondary aims are to
demonstrate feasibility and identify opportunities for integration into
routine care.
Precision Medicine Clinical Research Studies:
135-17 Caris Molecular Intelligence® and Caris Centers of Excellence
for Precision Medicine Network™ Outcomes Associated Repository
136-17 Caris Molecular Intelligence® and Caris Centers of Excellence
for Precision Medicine Retrospective Outcomes-Associated Database
167-17 Caris ctDNA Validation Project
179-17 Pharmacogenetics Program Pilot program to assess the potential role
of pharmacogenomics to improve drug safety in patients with advanced cancer.
204-17 Advance Treatment of Rare Tumors (tumor and normal tissue collection
for gene expression array, CGH, NGS, and blood for NGS testing)
101-18: Registry of patients in kindreds with germ-line TP53 mutations
(Li-Fraumeni)
For an up to date list of open clinical trials, contact Leila Andres,
M.S., at 888-862-5318.
""Hoag’s Precision Medicine Program has allowed us to identify
rare, actionable lung cancer mutations, such as HER-2 and EGFR Exon 20
insertion mutations, that confer resistance to both traditional chemotherapies
and even newer immunotherapies. In turn, patients from our local community
and around the world come to Hoag to benefit from clinical trial drugs
specifically targeting these and other lung cancer driver mutations."
Nishan Tchekmedyian, M.D.
Medical Oncologist
For more information call:
949-722-6237