Houston Methodist - Cancer Annual Report 2014-15

LEADING CANCER CARE & RESEARCH 2014-2015 YEAR IN REVIEW

Our commitment to advancing medicine with global impact begins in Houston, Texas, where we pioneer a better tomorrow through research, innovation and breakthroughs to rewrite the future of health.

THAT’S THE DIFFERENCE BETWEEN PRACTICING MEDICINE AND LEADING IT.

CONTENTS LEADING MEDICINE: AN OVERVIEW

02

ACCELERATING CURES FROM BENCH TO BEDSIDE

06

GROUNDBREAKING BREAST CANCER CLINICAL TRIALS

07

AGGRESSIVE TREATMENT FOR THE MOST AGGRESSIVE BREAST CANCER

08

HIGH-RISK PROGRAM IDENTIFIES CANCER RISK EARLY

09

EXPEDITING DRUG DEVELOPMENT FOR

10

EFFECTIVELY CAPTURING SINGLE CELLS

11

NOVEL IMMUNOTHERAPY RESEARCH

12

FUTURE CANCER TREATMENTS

TREATING OTHERWISE INOPERABLE CARDIAC TUMORS

BREAKTHROUGH DISCOVERY OF

14

COLORECTAL CANCER GENES

15

TARGETING TUMORS WITH UNPRECEDENTED ACCURACY

16

VISION-SAVING TREATMENT FOR OCULAR CANCERS

18

EDUCATING FUTURE CANCER LEADERS

20

8 21

16

02

PATIENT SATISFACTION: AMONG THE NATION’S BEST Houston Methodist Cancer Center has received some of the highest patient satisfaction scores in the nation. Feedback from our own patient surveys reveals similar positive results. In the words of our patients, the doctors, nurses and staff at Houston Methodist listen, explain things clearly and patiently, and treat them with courtesy and respect.

Independent surveys also support our achievements in patient satisfaction.

Press Ganey is a respected, independent consultant group that surveys approximately 1,700 U.S. hospitals in patient satisfaction.

Our commitment to our patients remains unconditional and unrestricted, heartfelt and genuine. Our determination to cure cancer is resolute, uncompromising and boundless. Together, this is a battle we will win.

2014 Patient Satisfaction Scores 100

94%

99%

91%

88% radiation oncology

Specialized oncologists partner with researchers to rapidly translate discoveries made in the laboratory into the clinical setting. Houston Methodist has recently developed the infrastructure to support multiphase clinical research.

Each cancer patient is distinct and requires individualized therapies. Our physicians have established a variety of specialized treatments that will aggressively target rapidly spreading or rare cancers. Our cancer-specific programs have a three-pronged goal: to reduce cancer development, to discover new therapeutic interventions for highly resistant cancers, and to provide personalized and complex treatments.

outpatient bone marrow transplant

Our oncologists bring the latest cancer treatments and therapeutic options to patients, often ahead of other institutions. We do this by leveraging our collaborative relationship with the Houston Methodist Research Institute, where teams of globally recognized researchers conduct studies in both basic and applied cancer research.

Our goal is to make our clinical trials available to every patient with a medical need who wishes to participate.

We now have the ability to create 3-D computer augmentations of virtual environments, which provide unique, new perspectives on the internal workings of the human body. We use bioinformatics to repurpose drugs approved for other diseases that have selective cancer-fighting properties, and we are pioneering work in the nanosyringe delivery of targeted drugs to cancers that are often refractory to conventional treatment.

inpatient bone marrow transplant

At Houston Methodist Cancer Center, a comprehensive, integrated team approach demonstrates our dedication to patients, which is further strengthened by an environment built upon the foundations of compassion and collaboration. We are committed to leading medicine through the administration of the best possible care, cutting-edge technological advances and our innovative explorations and development in clinical research. The cancer center currently ranks 36th out of more than 900 cancer centers in the nation in U.S. News & World Report.

infusion services

HOUSTON METHODIST CANCER CENTER

LEADING MEDICINE: CANCER CENTER OVERVIEW – 2014-2015

80

60

40

20

0

Source: Vizient (formerly UHC) is an affiliation of approximately 90 of the nation’s top nonprofit academic medical centers and their hospitals.

HOUSTON METHODIST CANCER CENTER VOLUMES

Inpatient Medical and Surgical Visits VISITS Houston Methodist Hospital TOTAL

Outpatient Visits

Patients

2,996

2,615

1,861 Surgical

Houston Methodist San Jacinto Hospital

104

98

75

2,520

Houston Methodist Sugar Land Hospital

378

720

235

Houston Methodist West Hospital

575

735

772

2,766

2013

2014

300

Houston Methodist Willowbrook Hospital

1,963

2,619

510

TOTAL

5,728

6,798

4,588

INFUSION

2013

2014

2015

Houston Methodist Hospital

6,136

8,249

7,531

Houston Methodist San Jacinto Hospital

36

18

34

Houston Methodist Sugar Land Hospital

880

828

750

31

55

106

Houston Methodist Willowbrook Hospital

1,897

1,082

852

TOTAL

8,980

10,232

9,273

2013

2014

2015*

22,507

23,087

15,981 Medical

7,068

7,273

5,390 Surgical

55

66

1,210 Medical

3

4

409 Surgical

92

206

2,932 Medical

200

MEDICAL AND SURGICAL VISITS

100

Houston Methodist Hospital

Prostate

2,626

2,565

Houston Methodist Hospital

Houston Methodist West Hospital

Breast

2,708

659 Medical

400

0

2015

151

600

2012

2014

131

Houston Methodist Hospital Top Five Tumor Sites: Three-Year Trend

500

2013

2014

2,696

2015

RADIATION THERAPY

2013

Bronchus & Lung

Colorectal

Blood & Bone Marrow

Houston Methodist San Jacinto Hospital Houston Methodist Sugar Land Hospital Houston Methodist West Hospital Houston Methodist Willowbrook Hospital TOTAL

16

15

1,208 Surgical

76

40

997 Medical

12

17

782 Surgical

11

17

1,545 Medical

1

4

813 Surgical

29,841

30,729

31,267

*January - September 2015

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04 HOUSTON METHODIST CANCER CENTER

NOTABLE APPOINTMENTS DARIO MARCHETTI, PHD

RANDA EL-ZEIN, MB, CHB, PHD

Dario Marchetti, PhD, is the first director of the newly created Center for Biomarkers. Prior to joining Houston Methodist, he spent seven years at Baylor College of Medicine making critical discoveries in the biology and clinical applications of circulating tumor cells (CTC), also known as “seeds” of metastatic disease.

Randa El-Zein, MB, PhD, is a research scientist who bridges the gap between clinical and investigative fields with extensive training in epidemiology, occupation health, and laboratory and medical science. In 2010, El-Zein and her team developed a novel cytokinesisblocked micronucleus assay (CBMN) that can measure susceptibility to lung cancer in high-risk individuals.

By capturing, isolating and interrogating CTCs from cancer patients, they have identified potential CTC biomarkers that may guide the treatment of breast cancer brain metastasis. Marchetti’s goal is to fully comprehend relationships between CTC-driven models of cell dormancy and the spread of cancer cells — fundamental aspects to understanding cancer recurrence and, notably, why and how CTCs can evade therapy and relapse despite clinical remission. The ultimate objective of the Center for Biomarkers is to evaluate CTC paths and one day create “liquid biopsy” assays for more precise cancer therapies.

Marchetti holds a degree in molecular biology from the University of Pavia, Italy. His bibliography includes 179 publications, of which 79 are in peer-reviewed journals in the fields of neuroscience and oncology. He has received numerous awards and secured uninterrupted National Institutes of Health (NIH) funding for 25 years as well as grants from state, institutional and private agencies. Marchetti serves on editorial boards of many journals; is a grant reviewing panel member for the NIH, the National Institutes of Health (Italy) and the U.S. Department of Defense, and is frequently invited as grant reviewer for national and international agencies devoted to oncology research.

Currently, El-Zein and her team are working to combine the standard features of mammography with identification of blood-based biomarkers that can more precisely indicate a woman’s risk for breast cancer-specific subtypes. The National Cancer Institute has awarded a grant of $2.8 million to El-Zein that will help support her groundbreaking efforts. If successful, the screening capabilities of mammography would be expanded into a true early detection device that would identify parenchymal hallmarks of precancerous change. El-Zein is collaborating with teams from The University of Texas MD Anderson Cancer Center and the University of Chicago.

El-Zein received her medical degree from Alexandria University in Alexandria, Egypt, and her PhD in human biological chemistry and genetics from The University of Texas Medical Branch in Galveston, Texas. El-Zein has published extensively on her work with lung cancer, breast cancer and the role of genetic susceptibility in the development of cancers such as Hodgkin’s lymphoma and gliomas.

COMMUNITY BREAST HEALTH INITIATIVES FOR THE UNDERSERVED Houston Methodist is dedicated to a healthier community through the provision of accessible care for the underserved.

We partner with Avon and Susan G. Komen to provide screenings and educate people on chronic disease prevention and treatment.

Breast Health Initiative

2,510 PATIENTS SERVED from April 1, 2014 – March 31, 2015

Continued Care in Breast Cancer Treatment and Participation in Clinical Trials

2,500 PATIENTS SERVED from April 1, 2014 – March 31, 2015

LETTER FROM THE DIRECTOR MOVING FORWARD WITH VISION The Houston Methodist Cancer Center continues its achievements within the expansive realm of cancer research and patient care. As always, the motivation and inspiration that propels this growth is the critical need to understand cancer and develop the therapies that will effectively treat it in all its pernicious forms. In our annual report, I am pleased to share some of our optimistic advancements within the past year in this fight to eradicate cancer.

Our patients provide a comprehensive trajectory for our areas of achievement and therapeutic discovery: how best to predict, how best to prevent, and how best to treat cancers that are refractory to conventional surgery, radiation and chemotherapy.

We are aggressively seeking effective therapies for triple negative breast cancer (TNBC), one of the most deadly and treatment-resistant cancers known. In one study, we are testing an investigational drug for the treatment of TNBC, which has been repurposed from a previous FDA-study for cardiology. In other studies, we are researching the properties of an immunotherapeutic agent that may potentially ease the therapeutic path for non-small-cell lung cancer (NSCLC), which accounts for approximately 85 percent of lung malignancies. And, yet another immunotherapeutic drug may benefit patients with treatment-resistant lymphomas.

New technology allows us to follow the path of radiation and will help to specify the exact area of malignancy, thereby improving the accuracy of treatment. We are also one of the few centers to customize ocular plaque radiotherapy.

Our High-Risk Program provides individuals who have an increased potential for cancer, through heredity or otherwise, with individualized screening plans and other options that will significantly narrow their risk of developing certain cancers. And, through genetic testing, we are more effectively targeting colorectal and other cancers.

We have spearheaded a collaboration with a number of high-profile medical centers to form the Consortium for the Advancement of Research Excellence (CARE). The goal of CARE is to fast-track the research-to-bedside process by capitalizing on the expertise and findings from top institutions throughout the nation. We also are working with Texas A&M University and Weill Cornell Medicine on educational initiatives to further research and develop methods that help accelerate translational medicine.

We look forward to the discoveries and developments that lie ahead. Thank you for your interest in the Houston Methodist Cancer Center. We hope you read more about our efforts to provide the best possible treatments for our patients.

Jenny Chang, MD Director, Houston Methodist Cancer Center Houston Methodist Hospital Professor of Medicine, Weill Cornell Medicine Full Member, Houston Methodist Research Institute

06 HOUSTON METHODIST CANCER CENTER

ACCELERATING CURES FROM BENCH TO BEDSIDE The Consortium for the Advancement of Research Excellence (CARE), a national multicenter collaboration spearheaded by researchers at the Houston Methodist Cancer Center, expedites the translation of basic cancer research into clinical practice by pooling the expertise and resources of some of the top research entities across the nation.

In addition to Houston Methodist Hospital, CARE member institutions include Case Western Reserve University, University of Miami, Weill Cornell Medicine, Emory University, University of Utah, Vanderbilt University, Northwestern University and Thomas Jefferson University.

“The goal of CARE is to bring cures to patients faster by making substantial changes in how we conduct cancer research,” said Jenny Chang, MD, director of the Houston Methodist Cancer Center.

40% OF ALL HOUSTON METHODIST CANCER CENTER clinical trials are investigator-initiated under CARE CARE currently has studies for breast cancer (Luminal A, Luminal B, Her2 overexpressed and triple negative) in all settings. Phase I studies for liquid and solid malignancies and several phase II studies are in development for gastric, GE junction, pancreas, lung and triple negative breast cancer.

Member institutions are developing a new model to implement effective, personalized therapy by incorporating innovative molecular diagnostics, targeted therapeutic interventions and advanced statistical trial design.

The consortium brings together expertise in cancer stem cells, genomics, tumor models, circulating biomarkers, novel biopsy techniques and drug development.

Investigators will have access to the pooled resources of a CARE tissue bank.

While each institute holds its own tissues, any investigator can submit a proposal to the CARE board for consideration for trial. The best proposals will be granted access to appropriate tissues from across the consortium.

CARE also simplifies and shortens some of the time-consuming steps that slow multicenter trial development. By offering institutional review board reciprocity among member institutions and streamlined contracts with funding agencies, CARE can bring trials to patients eight – 12 months faster.

Weill Cornell Medicine Thomas Jefferson University Case Western Reserve University Northwestern University University of Utah Vanderbilt University Houston Methodist Hospital Emory University University of Miami

CARE TRIAL ADDS POTENTIAL OPTIONS FOR HER2-POSITIVE BREAST CANCER The first CARE trial targets breast cancer and combines standard chemotherapy with two experimental agents — trastuzumab-emtansine (TDM-1) and lapatinib — to evaluate the effectiveness of this treatment in patients with newly diagnosed HER2-positive breast cancer.

As part of the trial, investigators will conduct a genomic study to identify critical molecular pathways that will help us design treatments that block drug resistance and control the disease.

By bringing this study and others like it to CARE, trials are quickly exposed to a larger group of patients, and patients benefit from a larger set of resources.

CARE’s structure also allows for multiple scientific reviewers to provide input on studies, which leads to a more effective study design, more robust trial goals and capabilities, and the highest level of patient safety.

“ The goal of CARE is to bring patients cures faster by making substantial changes in how we conduct cancer research,” Chang said.

NECTAR TRIAL Houston Methodist will be the lead site for a multicenter clinical trial called NECTAR, designed to test everolimus as a treatment for TNBC. Chang initiated the original pilot study that identified everolimus, a drug commonly used to treat kidney cancer, as a potential treatment for TNBC. The drug may stop the growth of TNBC tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor.

The Triple Negative Breast Cancer Program at Houston Methodist Cancer Center is designed to integrate care for all women diagnosed with TNBC, and our ongoing research is just one part of our commitment to fighting this most aggressive form of breast cancer.

Low-magnification scan of Triple Negative Invasive Breast Carcinoma

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08 HOUSTON METHODIST CANCER CENTER

THE MOST AGGRESSIVE TREATMENT FOR THE MOST AGGRESSIVE CANCER Researchers at Houston Methodist recently identified two genes that make triple negative breast cancer (TNBC) tumors treatment resistant and one of the most deadly breast cancers. Jenny Chang, MD, director of the Houston Methodist Cancer Center, and her team have initiated a clinical trial studying the efficacy of a drug that attacks the two genes — myeloid leukemia factor 2 (MLF2) and a ribosomal protein (RPL39) — which are involved in tumor initiation and metastases of TNBC. Findings from this trial were published in the June 2014 issue of the Proceedings of the National Academy of Sciences.

“This truly can be considered a breakthrough discovery in our work to eliminate TNBC, one of the most lethal forms of breast cancer. Targeting these two genes could improve patient outcomes for TNBC metastasis,” said Chang, principal investigator and last author of the study.

Notably, the investigational drug was repurposed from a compound that had been previously tested in a phase III study for cardiogenic shock and subsequently approved by the Food and Drug Administration. “Because we identified and repurposed an existing drug, we were able to develop it as an anticancer treatment in much less time and at a fraction of the cost,” said Chang.

THE STUDY INVOLVED COLLABORATION AMONG MANY SITES, INCLUDING • Chan Soon-Shiong Institute for Advanced Health Los Angeles, Calif.

• Five3 Genomics Santa Cruz, Calif.

• The University of Texas MD Anderson Cancer Center Houston, Texas • The University of Texas Health Science Center at San Antonio San Antonio, Texas • Greehey Children’s Cancer Research Institute San Antonio, Texas • Houston Methodist Research Institute Houston, Texas

• GEICAM Madrid, Spain

• Weill Cornell Medicine New York City, N.Y.

• Hospital Universitario Madrid Madrid, Spain

• Barts and the London NHS Trust London, UK

• Shanghai Cancer Center and Cancer Institute of Fudan University Shanghai, China

• Hospital Complex of Jaen Cordoba, Spain

• INEM Peru

HIGH-RISK PROGRAM IDENTIFIES CANCER RISK EARLY Physicians who are part of the High-Risk Program at Houston Methodist Cancer Center are experts in screening, diagnosing and treating patients at a high risk for cancer, including those who have hereditary cancer syndromes. Our genetic counselor is integrated into the clinic to provide patients with convenient access to genetic counseling services, tailored screening plans, targeted treatments and peace of mind.

Results of genetic testing, combined with family and personal histories, help the high-risk team personalize screening plans, medical treatments and surgical options to an individual’s cancer risk profile.

“At other centers, patients can wait up to six months for an appointment with a genetic counselor,” said Kate Dempsey, MS, certified genetic counselor at Houston Methodist Hospital. “At Houston Methodist, patients often can see a genetic counselor within a few days to discuss their personal risks of cancer.”

Identifying hereditary cancer syndromes is of the utmost importance for the highrisk team, as people with hereditary cancer syndromes may benefit from targeted cancer treatments. For instance, poly-ADP-ribose-polymerase (PARP) inhibitors can be offered to a patient with a diagnosis of ovarian cancer and an identified BRCA1 or BRCA2 mutation. In addition, tailored screening programs can greatly reduce an identified risk for developing cancer. Because hereditary cancer syndromes run in families, genetic counselors at Houston Methodist work with patients to get family members involved in preventive measures and possible treatment strategies.

“Understanding an individual’s risk for developing certain cancers can make a real difference in a patient’s overall survival and quality of life,” said Tejal Patel, MD, breast oncologist and director of the High-Risk Program. “We are committed to serving these patients with every tool available.”

Houston Methodist certified genetic counselor Kate Dempsey, MS, is integrated within the clinic to provide patients with convenient access to genetic counseling services.

“ Understanding an individual’s risk for developing certain cancers can make a real difference in a patient’s overall survival and quality of life,” said Tejal Patel, MD.

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10 HOUSTON METHODIST CANCER CENTER

SEEING FUTURE CANCER TREATMENTS IN DRUGS THAT ALREADY EXIST Houston Methodist researchers are driving a breakthrough strategy for safely expediting drug development. Researchers here have developed a proprietary technology platform, the DrugX engine, that helps repurpose FDA-approved medications or failed drugs that passed FDA phase I human safety trials to fight diseases that were not the drugs’ original targets. This greatly reduces the time and money it takes to get safe, effective drugs to patients.

“The cost of making new drugs is exorbitant, both financially and in terms of time.

By various accounts, it takes $1-2 billion and 14-17 years to develop a new drug today,” said Wong. “By identifying strong candidates for cancer treatments from among existing FDA-approved drugs, we avoid the costs and time associated with drug discovery and phase I trials. We also increase the odds of finding successful drugs because the safety and characteristics of these older drugs is well established.”

“We are able to bypass phase I trials, since the safety and toxicity of these older drugs are well established. This allows us to salvage hundreds of billions, if not trillions, of dollars of investment in drugs that failed over the past 50 years,” said Stephen Wong, PhD, the platform lead developer, holder of the John S. Dunn Presidential Distinguished Chair in Biomedical Engineering, chief research information officer, and founding chair of the Department of Systems Medicine and Bioengineering at Houston Methodist.

Ongoing drug repositioning studies at Houston Methodist

Houston Methodist supports novel research programs like this one to provide patients with viable treatments more quickly and with the same rigorous statistical and clinical research as the standard drug development model.

“DrugX is very much like a Google engine for drug discovery: it churns out targets and drugs for new diseases,” Wong said.

The Houston Methodist platform uses mathematical modeling, proprietary databases and supercomputers to sort through huge amounts of data to match more than 14,000 existing drugs, or combinations of drugs, to diseases for which they were not originally indicated. Once identified, the drugs are further validated through biological lab testing. A positive result means the drugs are ready for phase II human trials immediately, jumping past phase I studies.

• Formulation of biomarkers and drug cocktails targeting neurodegeneration, cancer and orphan diseases that require cost-effective solutions

• Active projects for finding cures for unmet needs, including Alzheimer’s disease; three rare childhood cancers, including medulloblastoma and Ewing’s sarcoma; and idiopathic pulmonary fibrosis

• A clinical study of a medication that may reduce diarrhea associated with

a major drug used to treat gastrointestinal cancer, especially in the elderly

“ DrugX is very much like a Google engine for drug discovery: it churns out targets and drugs for new diseases,” Wong said.

EFFECTIVELY CAPTURING SINGLE CELLS Lidong Qin, PhD, an associate professor in the Nanomedicine Department at Houston Methodist Research Institute, and his team have devised a unique technique that enables an ordinary pipette to pick up and transfer single cells. The handheld single-cell pipette — or hSCP — has two plungers. The first plunger withdraws fluid from a suspension of cells and can wash and separate the captured cell. The second plunger deposits the single cell into a growth medium or onto a slide for study.

Qin said one of his goals it to create this technology at a cost of $10 or less per run. Future designs of the hSCP will be developed with mass production in mind.

One of the challenges for single-cell research is the isolation of one cell from a collection of millions. Few technologies exist that allow researchers to withdraw single animal or bacterial cells from a tube. R&D Magazine named the hSCP as a finalist for the 53rd annual R&D 100 awards, which honor the 100 most innovative technologies and services of the past year.

12 HOUSTON METHODIST CANCER CENTER

NOVEL IMMUNOTHERAPY RESEARCH TO HELP THE BODY HEAL ITSELF REINVENTING NON-SMALL-CELL LUNG CANCER TREATMENT Physicians at Houston Methodist are studying an emerging immunotherapy drug that may simplify treatment for patients with non-small-cell lung cancer (NSCLC), which makes up about 85 percent of lung cancer cases.

Early research on the investigational drug has shown promising results and fewer toxic side effects than current chemotherapy treatments available. Eric Bernicker, MD, thoracic medical oncologist, is the study’s principal investigator at Houston Methodist. His research focuses on ways the immune system can be stimulated to destroy tumor cells, spare healthy tissue and improve patient survival using less toxic therapeutics.

“This is exactly what we want our research to bring to patients: effective cancer treatments without the harmful side effects of chemotherapy — thus enabling a good quality of life throughout treatment,” Bernicker said.

Immunotherapy stimulates the body’s own immune system to attack cancer cells using manmade proteins, or antibodies. This study, called the OAK study, uses an experimental antibody, which has shown promise in reducing tumor growth of melanoma and NSCLC. The OAK study is a global, open-label, randomized phase III study comparing MPDL3280A with chemotherapy agent docetaxel, intended to treat patients with locally advanced or metastatic NSCLC, following failure with platinum-based therapy. Patients in the study will be randomized 1:1 to docetaxel or MPDL3280A. As this is an open-label study, both the research physician and the patient will know which treatment is assigned.

“ We developed a novel investigational therapy directed at more universal tumor-expressed targets to make an immunotherapeutic intervention feasible in all treatment-resistant patients,”said Ann Leen, PhD, investigator with the Center for Cell and Gene Therapy.

NEW INTERVENTION MAY WEAKEN RESISTANT LYMPHOMA Researchers at Houston Methodist are testing an investigational immunotherapy to reduce the formidable, treatment-induced side effects suffered by patients with treatment-resistant Hodgkin lymphoma (HL) and non-Hodgkin lymphoma (NHL).

This investigator-initiated study is supported by the National Cancer Institute and the Center for Cell and Gene Therapy at Houston Methodist Hospital, Baylor College of Medicine and Texas Children’s Hospital.

For patients who are resistant to the standard treatment of chemotherapy and radiation, survival is low upon recurrence. Moreover, for patients who do respond, the standard treatment often can cause multiple comorbidities that greatly reduce quality of life and sometimes contribute to lower mortality from other diseases, such as heart disease.

Investigators at the Center for Cell and Gene Therapy have a history of success in removing roadblocks to treatment for these patients. As a precursor to this study, some of these same researchers discovered they could target the Epstein-Barr virus (EBV) with an immunotherapy, yielding success for treatment-resistant patients.

While this is a great improvement, not all HL and NHL tumors involve EBV, rendering EBV-targeted therapies ineffective.

“Based on the success of our previous research, we developed a novel investigational therapy directed at more universal tumor-expressed targets to make immunotherapeutic intervention feasible in all treatment-resistant patients,” said Ann Leen, PhD, investigator with the center.

The resulting study — administration of tumor-associated antigen (TAA)-specific cytotoxic t-lymphocytes to patients with active or relapsed hodgkin or non-hodgkin lymphoma (TACTAL) — uses the same successful immunotherapy, called (TAA)-specific cytotoxic T lymphocytes. It targets five proteins that appear on the surface of HL and NHL, much like EBV appears on the surface of some HL and NHL cells, to see if this technique provides similar results of improved survivability. The study will also evaluate whether this type of treatment reduces future complications associated with current standard treatment.

Houston Methodist supports novel research programs like this one to provide all patients with access to cures for cancer, furthering our goal to eliminate cancer in all its forms.

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14 HOUSTON METHODIST CANCER CENTER

TREATING OTHERWISE INOPERABLE CARDIAC TUMORS Cardiac autotransplantation is an advanced surgical technique that involves complete removal of the heart and provides an option for patients with left-sided cardiac tumors who previously had no surgical option. Cardiac sarcomas have been considered inoperable because vital organs and structures would be damaged using the most common, direct surgical approach to the heart.

During cardiac autotransplantation, the surgeon gains unique access to the left atrium. After putting the patient on cardiopulmonary bypass and then removing the heart, the surgeon resects the tumor, makes any necessary repairs to the heart structure, inspects the heart, great vessels and left atrium for tumor infiltration, and then implants the heart back into the patient.

Michael Reardon, MD, chief of cardiac surgery at Houston Methodist, has performed more cardiac autotransplants than any other surgeon in the world. A study led by Reardon shows that cardiac autotransplantation is a feasible and safe technique to treat malignant and complex benign left-sided cardiac tumors that are inaccessible via ordinary surgical resection.

Michael Reardon, MD, chief of cardiac surgery at Houston Methodist, has performed more cardiac autotransplants than any other surgeon in the world.

While extremely complex, the technique allows optimal anatomic exposure for complete resection and accurate reconstruction in the hands of a skilled and experienced surgical team. The study, which spanned 1998 to 2013 at Houston Methodist and involved 35 cardiac autotransplants performed on 34 patients, was published in the September 2014 issue of the Annals of Thoracic Surgery.

DISCOVERY OF COLORECTAL CANCER GENES PUTS EFFECTIVE TREATMENTS CLOSER A breakthrough discovery of a set of genes will help drive the development of more targeted therapies to end colorectal cancer (CRC) and possibly other cancers.

The new findings from the lab of Houston Methodist genetics researchers Neal Copeland, PhD, and Nancy Jenkins, PhD, offer unprecedented understanding of the growth, metastasis and repression of the disease.

The newly identified genes provide researchers with specific targets for developing drugs that can stop or slow tumor progression and encourage tumor suppression.

“By advancing the understanding of the developmental dynamics of CRC, this discovery can help fuel multiple paths of cancer research, moving us closer to our goal of putting an end to cancer,� Copeland said.

Jenkins, Copeland and their team introduced unique, synthetic DNA sequences into murine models in the lab. By manipulating DNA in the models, the team was able to identify six genes driving malignant tumor growth and a new human CRC suppressor gene, ZNF292, which may also affect other cancers.

Houston Methodist genetics researchers Neal Copeland, PhD, (left) and Nancy Jenkins, PhD, (center) offer unprecedented understanding of the growth, metastasis andhoustonmethodist.org/cancer repression of the disease.

16 HOUSTON METHODIST CANCER CENTER

TARGETING TUMORS WITH UNPRECEDENTED ACCURACY Houston Methodist soon will be the only hospital in Houston to offer new technology that allows physicians to see — in real time — exactly where radiation is being delivered so therapy can be fine-tuned during the procedure, making treatment as accurate as possible and reducing complications.

Using continuous visualization, our physicians can further reduce the risk of irradiating healthy tissue since the patient’s respiratory process subtly changes the location of the tumor with each breath.

“We can pinpoint radiation delivery in the midst of anatomical movement, sparing healthy tissue and shortening treatment by weeks,” said Brian Butler, MD, chair of the Department of Radiation Oncology at Houston Methodist. “In some cases, we can reduce radiation days from an industry standard of 39 to only five days because of better targeting.”

“We can pinpoint radiation delivery in the midst of anatomical movement, sparing healthy tissue and shortening treatment by weeks,” said Brian Butler, MD, chair of the Department of Radiation Oncology at Houston Methodist. “In some cases, we can reduce radiation days from an industry standard of 39 to only five days because of better targeting.”

The technology also allows physicians at Houston Methodist to understand how healthy structures can move into the radiation beam during treatment. This is a significant advancement, as patients are traditionally imaged only at the beginning of treatment to evaluate if the target is being hit. We now safely image throughout treatment, gaining a more strategic understanding of the whole process, while using magnetic resonance imaging (MRI) technology that does not expose the patient to added detrimental effects of radiation. In addition, we can turn off the beam if it is not hitting the target and turn it on when the tumor moves into the planned location.

Certain parts of the anatomy are more prone to movement while patients inhale and exhale, such as the prostate, liver and lungs. Beginning in 2016, radiation oncologists at Houston Methodist Hospital will use a new MRI-guided system to treat patients with prostate cancer and will then expand its usage to treat other cancers.

CANCER CONNECTION, THE HOUSTON METHODIST CANCER CENTER'S PHYSICIAN E-NEWSLETTER Hundreds of oncologists in the United States read Cancer Connection. Earn CME credit while accessing the work of leading clinicians and researchers and learn about leading-edge discoveries, innovations, procedures and treatments for cancer.

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18 HOUSTON METHODIST CANCER CENTER

HIGHLY SPECIALIZED OCULAR TEAM OFFERS ONLY VISION-SAVING TREATMENT FOR SOME CANCERS A team of ocular cancer specialists at Houston Methodist Cancer Center offers rare subspecialty expertise in ocular cancers, including experience in personalized ocular plaque radiotherapy, which is the only visionsaving treatment for uveal melanoma and other eye tumors.

EXTENDING SURVIVAL THROUGH GENOMIC PROFILING OF EYE CANCERS

This delicate procedure involves use of a customized disc, or plaque, with small radioactive beads, that destroys the tumor. The cancer center is one of only a few in the nation with a team of specialized radiation physicists who can customize the plaque to the individual patient’s eye and tumor. Customization reduces radiation exposure, increases accuracy of treatment and reduces discomfort.

Patients with ocular melanomas often experience metastasis to the liver. On average, approximately 50 percent of patients develop metastatic disease. Of those, 85 to 90 percent of the metastases are in the liver. If caught early, liver metastases can be treated with surgery and chemotherapy. Our use of genomic profiling highlights those most at risk for uveal melanoma metastases to the liver and helps our care team determine how and how often to screen patients to catch metastases while they are still treatable.

Amy Schefler, MD, ocular oncologist and vitreoretinal surgeon at Houston Methodist, is an expert in the field of ocular plaque radiotherapy. During surgery, she implants the plaque onto the surface of the patient’s eye using ultrasound imaging and transillumination analysis. This ensures that the plaque covers all margins, and avoids critical structures in the eye.

Over time, the beads release radiation into the tumor to eradicate it. The surgeon removes the plaque within approximately one week, depending on the tumor’s size, location and other characteristics.

Houston Methodist uses genomic profiling of ocular tumors to tailor postsurgical care for our patients with the goal of catching metastases early and improving survival.

RESEARCH TO DIRECTLY BENEFIT PATIENTS As part of our goal to end cancer and provide the best results possible for our patients, Houston Methodist researchers are actively engaged in reshaping the future of ocular cancers. We currently offer several ongoing clinical trials to reduce radiation retinopathy, which causes vision loss and is the most common side effect of eye cancer treatments.

“Because of our team’s high level of experience and specialization, our patients experience almost no local recurrence after treatment,” Schefler said.

Houston Methodist Cancer Center is one of only a few centers in the nation with a team of specialized radiation physicists who can customize the plaque to the individual patient’s eye and tumor.

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20 HOUSTON METHODIST CANCER CENTER

HEMATOLOGY-ONCOLOGY FELLOWSHIP PROGRAM DEVELOPS CANCER LEADERS The Houston Methodist Hematology-Oncology Fellowship Program is designed to develop the careers of future leaders through mentorship, comprehensive education and training in clinical practice and research.

ELEVATING ACADEMIC TRAINING THROUGH THE STUDY OF TRANSLATIONAL MEDICINE Houston Methodist recently formed a collaboration with Texas A&M Health Science Center to create new hands-on education programs for Texas A&M graduate and medical school students as they work alongside physician researchers, scientists and engineers at Houston Methodist during their training.

Texas A&M students practice translational and clinical research and medicine at Houston Methodist during their rotations and thesis work in the Texas Medical Center. Seven MD/PhD students complete a summer rotation, which is a PhD requirement. The new programs will teach the art and science of translational medicine as a core principle of clinical practice and medical research.

Just as we have focused our research on translating innovations into real clinical applications, we are expanding our educational programs in the translational medicine field to train future leaders in academic medicine.

The program, inaugurated in July 2014, encompasses training in cancer prevention, clinical cancer genetics, evidence-based patient care and patient-based translational and clinical research. Fellows can customize their training for career tracks in clinician-in-community practice, clinician educator or clinician-researcher-inacademic practice.

For the 2015-2016 academic year, Houston Methodist accepted 1 percent of all applicants who applied to the fellowship program. The two positions were filled by our top five ranked candidates.

Program Director Alexandria T. Phan, MD, is an associate member of the Houston Methodist Research Institute and associate professor at Weill Cornell Medicine.

She is a medical oncologist with research focus and clinical practice specializing in gastrointestinal malignancies. She joined Houston Methodist Hospital in 2013, and is nationally and internationally recognized for her expertise in neuroendocrine tumor and adrenal malignancies. Phan has more than a decade of experience as a gastrointestinal oncologist and continues to have active research collaborations here and abroad.

Houston Methodist accepted 1 percent of all applicants who applied for the fellowship program.

AN ACCELERATED CAREER PATH IN CANCER RESEARCH Houston Methodist Hospital and Weill Cornell Medicine are collaborating on a unique educational initiative called the Mentored Clinical Research Training Program (MCRTP), which is a fast-‐track program for junior physicians at Houston Methodist and Weill Cornell to learn how to develop clinical research proposals and embark on research career pathways.

“This program gives busy practicing physicians an accelerated, intensive jumpstart on a career path in clinical research,” said Timothy Boone, MD, PhD, co-director of the Institute for Academic Medicine at Houston Methodist Hospital.

The MCRTP begins with a rigorous, four-day workshop held in New York City.

Drawing on courses adapted from the WCM Clinical and Translational Science Center, contribution from the Houston Methodist Research Institute, small group

sessions and invited speakers, the workshop provides an introduction to the foundations of clinical research, including research design and methodologies, data management and analysis, and the regulatory process.

Throughout the subsequent year, trainees develop clinical research proposals under mentorship from experienced clinical researchers at Houston Methodist and WCM. The final product is an IRB‐ submission-ready research proposal that is sent to an external funding agency for consideration.

The program, which started in 2013, is limited to 10 total trainees per year, chosen based on the quality of their proposals and backgrounds.

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22 HOUSTON METHODIST CANCER CENTER

HOUSTON METHODIST: GLOBAL EDUCATIONAL REACH 2015 HOUSTON METHODIST STATISTICS

RESEARCH EDUCATION LEARNERS: 363 128 Postdoctoral trainees 112 Graduate students 63 Summer students 6 Undergraduate students 7 High school students

CONTINUING MEDICAL EDUCATION PHYSICIAN LEARNERS: 10,141 103 Courses

GRADUATE MEDICAL EDUCATION 2015 residents: 262 2018 fellows: 303

GLOBAL HEALTH CARE SERVICES LEARNERS: 1,207 29 countries

697 CME credit hours awarded 8 International partnerships 58 Institutions 16 Lectures

HOUSTON METHODIST INSTITUTE FOR TECHNOLOGY, INNOVATION & EDUCATIONâ„ 2006-2014 learners: 35,000 2015 learners: 6,697 554 courses

OTHER LEARNERS Rotating residents: 430 Nursing students: 1,191 Pharmacy students: 315 Allied health students: 141

THE WORLD’S FIRST VIRTUAL INTELLIGENCE FOR THE OPERATING ROOM The Houston Methodist Institute for Technology, Innovation & Education℠SM, known as MITIE — one of the largest and most comprehensive education facilities in the world — is a place where surgeons and other health care providers continually refine their skills and acquire new expertise to perform at optimal levels throughout their careers.

“Currently, surgeons cannot track multiple technologies or see what is happening in the body during surgery in a satisfactory way because a system that can analyze overlapping technologies has not been developed yet,” Dunkin said. “RETINA brings the information together, analyzes it, and provides the surgeon with the necessary, real-time information.”

To address the challenges of the modern operating room (OR), physicians and researchers at MITIE are designing a virtual intelligence system. The complexity of larger medical teams and overlapping technologies in the OR requires surgeons to interpret and evaluate an abundance of data while performing surgical procedures. To improve performance and decrease variability, the Intelligent OR brings surgeons and computational scientists together to develop safer, more accurate methods of managing patient care in real time.

The Intelligent OR also houses the Smart OR, a group of sensors placed at specific locations of the OR that automatically detect key steps of the surgery, such as when a patient is brought in and moved out of the room.

“In today’s operating room, we are overwhelming surgeons with information from multiple technology platforms and staff who can distract them from the procedure at hand,” said Brian Dunkin, MD, a Houston Methodist endoscopic surgeon and medical director of MITIE. “The Intelligent OR is designed to provide surgeons and staff with necessary information at the point of care without unneeded distractions.”

Inside the Intelligent OR is the Smart Trocar, a device with a small camera that can attach to a traditional laparoscopic trocar and connect to a Real-time Interactive Navigation Assistance (RETINA) system. RETINA uses multiple technologies to track changes in the body during surgery. In most cases, each step of an operation requires a different surgical tool. The Smart Trocar and RETINA work in concert to track tools identified by a unique color. With this, the RETINA system can track the progress of a surgery.

“By adding sensors to the operating room, we are able to track a variety of data points,” said Marc Garbey, PhD, research director of MITIE and professor of computational science at the University of Houston. “We believe the ability to track instrumentation and movement in the operating room will increase efficiency and reduce costs.”

Intelligent OR technology will help surgeons perform operations and image-guided procedures more efficiently and accurately. Incorporation of an intelligence system that combines and computes essential OR data will allow surgeons to focus on the patient and the operation in the provision of an unparalleled level of care.

houstonmethodist.org/cancer

24 HOUSTON METHODIST CANCER CENTER

HOUSTON METHODIST: BUILDING A LEGACY OF INGENUITY From humble beginnings as a 30-bed hospital more than 90 years ago, Houston Methodist has evolved into one of the nation’s largest private nonprofit hospitals, an academic medical center and a center for visionary medical research.

Our reputation for excellence in patient care and commitment to improving outcomes represent a significant motivation in the development of six Houston Methodist Cancer Center locations in the Greater Houston area: • Houston Methodist Hospital - Texas Medical Center • Houston Methodist San Jacinto Hospital • Houston Methodist Sugar Land Hospital • Houston Methodist West Hospital

Together, we collaborate to advance clinical medical research and train the next generation of physicians and researchers.

For Houston Methodist clinicians and researchers, leading medicine is a call for excellence in every aspect of patient care. We consistently rank in U.S. News & World Report’s “Best Hospitals” list. The 2015 issue named Houston Methodist among the country’s top hospitals in 11 specialties, No. 1 in the metro area and No. 1 hospital in Texas. Additionally, Houston Methodist unfailingly achieves Magnet® distinction for exceptional nursing. Our research ranks in the top 20 for federal funding, and supports early phase clinical trials and FDA-certified manufacturing for research. Because of this commitment to excellence, the finest researchers and clinicians are joining us to accelerate the discovery and delivery of better care and better cures. That’s the difference between practicing medicine and leading it.

• Houston Methodist Willowbrook Hospital • Houston Methodist The Woodlands Hospital (opening in 2017) Primary academic affiliates of Houston Methodist are top-ranked Weill Cornell Medicine and NewYork-Presbyterian Hospital. Houston Methodist also has affiliations with The Texas A&M University System and the University of Houston.

MORE THAN 790 clinical studies and trials $130 MILLION total research portfolio

2015 HOUSTON METHODIST STATISTICS

2,043 OPERATING BEDS

101,508

814,309

12,406

297,906

INPATIENTS

OUTPATIENT

INTERNATIONAL PATIENT ENCOUNTERS (from 84 foreign countries)

EMERGENCY ROOM VISITS

VISITS

4,500

603

36

AFFILIATED PHYSICIANS

FACULTY

RESIDENCY

44 GME

PROGRAMS

PROGRAMS

LEADERS IN RESEARCH At Houston Methodist, we are dedicated to defining the future of medicine. We engineer discoveries in the lab to become clinically useful products, channel the best innovations through early-stage clinical trials, and actively transition those innovations to our industry partners. Our commitment to the full cycle of discovery and delivery sets us apart as leaders who provide patients from around the world access to the latest health care advances.

Visit houstonmethodist.org/research to see all the ways we’re leading research. Š2015 Time Inc. FORTUNE and 100 Best Companies to Work For are registered trademarks of Time Inc. and are used under license. FORTUNE and Time Inc. are not affiliated with, and do not endorse products or services of Houston Methodist.

Houston Methodist Hospital 6565 Fannin St., Houston, TX 77030 877.790.DOCS

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LEADING MEDICINE YESTERDAY, TODAY AND TOMORROW At Houston Methodist, we have a proud tradition of revolutionizing medicine. Our past achievements have built a legacy that spans multiple decades and disciplines, and that same culture of excellence inspires us to be the pioneers of tomorrow.