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Harnessing the Power of Precision Oncology Cancer Advances Cleveland Clinic Cancer Center | Winter 2019 Harnessing the Power of Precision Oncology Ranked No. 5 in America for cancer care by U.S. News & World Report. Dear colleagues, Welcome to this issue of Cancer Advances. Our cover story features a sampling of our work in genetics and Advancing genomics, which is shifting the focus of questioning in oncologic research and care from tumor location to genetic mutation. Our researchers are approaching questions of cancer genetics from across the continuum, including detecting cancers at an earlier stage (p. 4), best Precision practices in testing for non-small cell lung cancer (p. 6), expanding the use of predictive assays (p. 7), treatments targeting individual tumor DNA (p. 8) and a new National Cancer Institute grant to study response prediction in Oncology radiation oncology (p. 10). Our leadership in developing the accreditation program for rectal cancer (p. 22) and the continued relevance and from Risk Prediction utility of the Khorana score (p. 14) showcase our ability to determine the line of inquiry at the national level. to Treatment Response Our multidisciplinary Sarcoma Program continues to investigate better treatments for this rare cancer while providing patients with a level of expertise matched by few centers in the United States (p. 16). Our work on potential new therapies for acute myeloid leukemia (p. 20) and breast cancer (p. 13) demonstrates the promising results of the continued pursuit of inquiry for our patients. Finally, we demonstrate our ability to ask complex questions with the work we’re pursuing on laser interstitial therapy with colleagues in the Rose Ella Burkhardt Brain Tumor and Neuro-Oncology Center (p. 24). I hope this issue of Cancer Advances sparks new insights into your research and clinical questions, and I welcome the opportunity to collaborate, to discuss new ideas and to answer your questions, from bench research to clinical trials to operations and strategies for optimal clinical alignment. If we can help you with a patient’s care or a clinical issue, please let me know. Sincerely, Brian J. Bolwell, MD, FACP Chairman, Taussig Cancer Institute Cleveland Clinic Cancer Center [email protected] | 216.444.6922 On Twitter: @BrianBolwellMD Cleveland Clinic Cancer Center | Care that’s personal. Research that’s revolutionary. Cancers are increasingly seen as diseases of the genome. The characterization of genetic and protein abnormalities now often determines how cancers are diagnosed and treated. Precision oncology uses genetic information from an individual’s Cleveland Clinic’s Charis Eng, MD, PhD, cancer to determine the most effective treatment, and allows the use of an agent and former Vice President Joe Biden targeted to that specific genetic abnormality. receive the 2018 Medal of Honor from the American Cancer Society...11 This increasingly complex and variable picture of cancer further underscores the need for innovative responses. Novel approaches are essential in every realm of cancer care: genomic data collection and analysis; drug development; clinical trial Table of Contents design; surgery, radiation and chemotherapeutics; cost reimbursement strategies; ADVANCING PRECISION ONCOLOGY research funding. Detecting Early-Stage Cancers Circulating Cell-Free Genome Atlas Substudy Fortunately, there is no shortage of inventive work underway when it comes to Demonstrates Project’s Potential to Map Cancer cancer care. Cleveland Clinic’s strong clinical genomics program, housed in the Genetics...4 Center for Clinical Genomics, enhances the Cancer Center’s efforts to harness Best Practices in Testing Next-Generation Sequencing Saves Time and precision oncology for the benefit of patients. Many tumors undergo testing for Money for Treatment of Metastatic Non-Small Cell genomic alterations, which are then reviewed by the Genomics Tumor Board, a Lung Cancer...6 regular meeting with various oncologists, translational scientists, pathologists and Expanding the Use of Predictive Assays Multigene Assay Holds Prognostic Promise for genetic counselors. Renal Cell Carcinoma...7 Experts then alert each patient’s physician to recommended, individualized Treatments Targeting Individual Tumor DNA ALLELE: Guiding Glioblastoma Treatment with treatment options, as well as to clinical trials for which the patient might be an Tumor Genetics...8 appropriate candidate. Every eligible patient is offered tumor genomic profiling. Predicting Responses to Therapy Abazeed Receives $2 Million Grant to Study Role “It’s a very exciting time. Personalized cancer medicine is real,” says Brian Bolwell, of Genetic Composition in Predicting Radiation MD, Chair of Cleveland Clinic’s Taussig Cancer Institute. “It’s not theoretic; it’s Therapy Efficacy...10 happening today in clinic. In some cancers for which we didn’t have much to offer patients 10 to 15 years ago, we now have targeted therapies that are extending T-DM1 + Neratinib’s Safety and Efficacy their lives and giving them a good quality of life as well.” in Women with Metastatic HER2+ Breast Cancer...13 The following projects demonstrate a sampling of Cleveland Clinic’s expertise across The Khorana Score, 10 Years Later...14 the continuum, from prediction and prevention to diagnosis and treatment. Sarcoma: Rare, Complex, Approachable with Appropriate Care...16 VeloSano: 100% for the Cure...19 How Nucleophosmin Mutation Causes Acute Myeloid Leukemia...20 Developing the National Accreditation Program for Rectal Cancer...22 Tumor Ablation with Chemo-Radiotherapy Consolidation Yields Rare Durable Remission of Glioblastoma...24 New Staff...26 Chairman’s Q&A: Cultivating Emotional Intelligence Through Asking Questions...26 Resources for Physicians...28 Cover image: The work of researcher and radiation oncologist Mohamed Abazeed, MD, PhD, explores whether the genetic composition of lung cancer cells can predict response to radiotherapy. Dr. Abazeed recently received a $2 million grant from the National Cancer Institute for this research. 2 | 3 | clevelandclinic.org/cancer CANCER ADVANCES WINTER 2019 ADVANCING PRECISION ONCOLOGY Detecting Early-Stage Cancers Circulating Cell-Free Genome Atlas Substudy Demonstrates Project’s Potential to Map Cancer Genetics Dr. Klein is Chair of Cleveland Clinic researchers are helping NCT02889978 at a glance Cleveland Clinic Glickman build a database that could lead to the Urological & Kidney The observational study, funded by GRAIL Inc., has so Institute and Professor of development of a blood test for early-stage far enrolled > 11,000 of 15,000 planned participants (70 Surgery at Cleveland Clinic cancer and promises to shed new light on percent with cancer, 30 percent noncancer) in order Lerner College of Medicine. the biology of cancer at its initial stages. to characterize the population variation in cancer and He can be reached Results of a preplanned substudy of this at [email protected] or noncancer subjects. The research team will use deep 216.444.5591. multicenter clinical trial — the Circulating sequencing of cell-free nucleic acids in the blood, an On Twitter: @EricKleinMD Cell-Free Genome Atlas (CCGA) — were emerging biomarker for earlier cancer detection, to presented at the 2018 American Society of develop a detailed atlas of cancer genetics. Clinical Oncology (ASCO) meeting. The Center for Clinical Genomics team, along with primary investigators Eric A. Klein, MD, Chair of Cleveland Clinic Glickman Urological & Kidney Institute, and Mikkael Sekeres, MD, MS, Director of Cleveland Clinic Cancer Center’s Leukemia Program, will help recruit more than 1,000 Cleveland Clinic patients over the age of 20. “The complex nature of cancer makes it difficult to identify biomarkers for detection of early-stage cancer before symptoms appear,” says Dr. Sekeres. “The CCGA study will expand our knowledge about genomic pro- files in cancer patients.” Substudy methods and results The preplanned substudy of 1,627 participants collected blood from 878 participants with newly diagnosed, untreated cancer (20 tumor types, all stages) and 749 participants with no cancer diagnosis (controls) for plasma cell-free DNA (cfDNA) extraction. The team performed three prototype sequencing assays: paired cfDNA and white blood cell (WBC) targeted sequenc- ing (507 genes, 60,000X) for single nucleotide variants/ indels, cfDNA whole genome bisulfite sequencing (30X) for methylation, and paired cfDNA and WBC whole- genome sequencing (30X) for copy number variation. WBC sequencing identified the contribution of clonal hematopoiesis. Cleveland Clinic Cancer Center | Care that’s personal. Research that’s revolutionary. CLEVELAND CLINIC CANCER CENTER | CANCER ADVANCES Dr. Sekeres is Director of Cancer Advances provides information from Cleveland Clinic Cancer Cleveland Clinic cancer specialists about Center’s Leukemia innovative research and diagnostic and Program and Professor management techniques. of Medicine at Cleveland Please direct correspondence to: Clinic Lerner College of Taussig Cancer Center / CA Medicine. Cleveland Clinic 9500 Euclid Ave. He can be reached at Cleveland, OH 44195 [email protected] or Cleveland Clinic Cancer Center annually serves 216.445.9353. thousands of cancer patients. More than 450 On Twitter: clinicians, scientists and other cancer specialists @MikkaelSekeres are committed to researching and applying the latest, most effective techniques for diagnosis and treatment to achieve long-term survival and improved quality of life for all cancer patients. Cleveland Clinic Cancer Center
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