Genetic Tests for Cancer Diagnosis

CMS evidence review | evidence_type=MEDCAC Meeting | record_type=medcac_meeting | document_id=67 | meeting_date=2013-05-01

The Secretary's Advisory Committee on Genetics, Health and Society (SACGHS) has defined genetic testing as "…any test performed using molecular biology methods to test DNA or RNA, including germline, heritable, and acquired somatic variations." CMS has commissioned technology assessments (TAs) on two types of genetic tests. The first TA examined DNA- or RNA-based tests which are likely to predict the tissue of origin in patients presenting with a cancer of unknown primary site (CUP). The second TA examined fluorescent in-situ hybridization (FISH) tests for cancer/pre-cancer in patients with atypical squamous cells of unknown significance (ASCUS) or low-grade squamous intraepithelial lesions (LSIL) in cytological specimens from the uterine cervix. CMS will convene the panel to consider the evidence about these two types of genetic tests for cancer diagnosis.

Actions Taken: February 13, 2013 CMS posts MEDCAC meeting announcement. February 27, 2013 Posted FR notice. March 5, 2013 Posted questions to panel. April 1, 2013 Posted Technology Assessments ( Fluorescence In Situ Hybridization (FISH) or Other In Situ Hybridization (ISH) Testing of Uterine Cervical Cells to Predict Precancer and Cancer ; Genetic Testing or Molecular Pathology Testing of Cancers with Unknown Primary Site to Determine Origin ) for meeting. April 26, 2013 Posted materials for meeting: agenda , roster , speakers list , presentations and written comments . May 06, 2013 Posted scoresheet from meeting [PDF, 23KB]. May 30, 2013 Posted transcript [PDF, 289KB] and minutes [PDF, 252KB] from meeting. Information about visiting CMS Driving directions to CMS Recommended hotels Agenda: Federal Register Notice Agenda Medicare Evidence Development & Coverage Advisory Committee May 1, 2013 7:30 AM – 4:30 PM CMS Auditorium Rita Redberg, MD, MSc, Chair Art Sedrakyan, MD, PhD, Vice Chair James Rollins, MD, PhD, Director, Division of Items and Devices, Coverage and Analysis Group Maria Ellis , Executive Secretary 7:30 – 8:00 AM Registration 8:00 – 8:10 AM Opening Remarks— Maria Ellis/James Rollins, MD/Rita Redberg, MD 8:10 - 8:20 AM CMS Presentation & Voting Questions – Chuck Shih, PhD 8:20 – 8:50 AM TA Presentation: Sreelatha Meleth, PhD, Senior Research Statistician Social Statistical and Environmental Sciences, RTI International and Nedra Whitehead, PhD, MS, CGC, Senior Genetic Epidemiologist, Statistics and Epidemiology, RTI International 8:50 – 9:10 AM Barbara Conley, MD, Associate Director, Cancer Diagnosis Program, Division of Cancer Treatment and Diagnosis, National Cancer Institute 9:10 – 9:40 AM TA Presentation: Katrin Uhlig, MD, MS, Attending Physician, Division of Nephrology, Tufts Medical Center, Associate Professor, Tufts University School of Medicine 9:40 – 10:00 AM Dorothy L. Rosenthal, MD, FIAC, Professor of Pathology, Oncology and Gynecology/Obstetrics, Johns Hopkins School of Medicine 10:00 – 10:15 AM BREAK 10:15 – 11:00 AM Scheduled Public Comments (Refer to Speaker List) Public attendees, who have contacted the executive secretary prior to the meeting, will address the panel and present information relevant to the agenda. Speakers are asked to state whether or not they have any financial involvement with manufacturers of any products being discussed or with their competitors and who funded their travel to this meeting. 11:00 – 11:15 AM Open Public Comments Public Attendees who wish to address the panel will be given that opportunity 11:15 – 12:00 PM Questions to Presenters 12:00 – 1:00 PM LUNCH (on your own) 1:00 – 2:00 PM Initial Open Panel Discussion: Dr. Redberg 2:00 – 3:00 PM Formal Remarks and Voting Questions The Chairperson will ask each panel member to state his or her position on the voting questions. 3:00 – 4:00 PM Final Open Panel Discussion: Dr. Redberg 4:00 – 4:30 PM Closing Remarks/Adjournment: Dr. Rollins & Dr. Redberg Issue: The Secretary's Advisory Committee on Genetics, Health and Society (SACGHS) has defined genetic testing as "…any test performed using molecular biology methods to test DNA or RNA, including germline, heritable, and acquired somatic variations." CMS has commissioned technology assessments (TAs) on two types of genetic tests. The first TA examined DNA- or RNA-based tests which are likely to predict the tissue of origin in patients presenting with a cancer of unknown primary site (CUP). The second TA examined fluorescent in-situ hybridization (FISH) tests for cancer/pre-cancer in patients with atypical squamous cells of unknown significance (ASCUS) or low-grade squamous intraepithelial lesions (LSIL) in cytological specimens from the uterine cervix. CMS will convene the panel to consider the evidence about these two types of genetic tests for cancer diagnosis. Minutes: Download meeting minutes [PDF, 252KB] Other Material: Transcript 1 Presentations Written Comments Panel Voting Questions: May 1, 2013 MEDCAC Selected Genetic Tests for Cancer Diagnosis and Treatment Selection On May 1, 2013, the Medicare Evidence Development and Coverage Advisory Committee (MEDCAC) will consider evidence about two types of genetic tests used for cancer diagnosis: DNA- or RNA- based tests to predict the likely tissue of origin in patients presenting with a cancer of unknown primary site (‘CUP’ tests); and Fluorescent in-situ hybridization (‘FISH’) tests for cancer/pre-cancer in patients with atypical squamous cells of unknown significance (ASCUS) or low-grade squamous intraepithelial lesions (LSIL) in cytological specimens from the uterine cervix. Outcomes of interest for CMS of FISH are histologic confirmation of higher-grade cervical intraepithelial neoplasia ('CIN') on biopsy, overall survival, mortality, avoidance of harms of anti-tumor treatment, quality of life and others. Outcomes of interest for CMS of CUP are tumor recurrence, overall survival, mortality, avoidance of harms of anti-tumor treatment, quality of life, and others. For each part of voting questions 1-3 below, please use the following scale identifying your level of confidence - with a score of 1 being low or no confidence, and 5 representing high confidence. 1 — 2 — 3 — 4 — 5 Low Intermediate High Confidence Confidence Confidence Voting Questions 1. How confident are you that existing evidence is sufficient to confirm the clinical validity (defined as how reliably test results is associated with the presence of the disease or target condition) of each of the following? DNA- or RNA-based testing to predict tissue of origin for CUP. ‘FISH’ testing for cervical cancer/pre-cancer in patients with atypical squamous cells of unknown significance (‘ASCUS’) / low-grade intraepithelial squamous lesion (‘LSIL’). If the answer for either part of Question 1 is at least in the ‘Intermediate’ range (mean score is 2.5 or more) please vote on the corresponding part(s) of question 2. If not, please discuss questions 4-6. 1 — 2 — 3 — 4 — 5 Low Intermediate High Confidence Confidence Confidence 2. How confident are you that there is sufficient evidence to determine whether genetic testing of tumor tissue affects health outcomes (including benefits and harms) for patients with cancer whose anticancer treatment strategy is guided by the results of each of the following? DNA- or RNA-based testing to predict tissue of origin for CUP. FISH testing for cervical cancer/pre-cancer in patients with ASCUS/LSIL. If the answer for either part of Question 2 is at least in the ‘Intermediate’ range (i.e., mean score is 2.5 or more) please vote on the corresponding part(s) of question 3. 1 — 2 — 3 — 4 — 5 Low Intermediate High Confidence Confidence Confidence 3. How confident are you that there is sufficient evidence to conclude that genetic testing of tumor tissue improves overall health outcomes (including benefits and harms) for patients with cancer whose anticancer treatment strategy is guided by the results of each of the following? DNA- or RNA-based testing to predict tissue of origin for CUP. FISH testing for cervical cancer/pre-cancer in patients with ASCUS/LSIL. 1 — 2 — 3 — 4 — 5 Low Intermediate High Confidence Confidence Confidence Discussion Questions 4. Please discuss whether the evidence as presented may be generalized based on each of the following factors: Regulatory status of test (e.g., FDA approved/cleared vs. laboratory-developed test)? Site of testing (e.g., university medical center or commercial laboratories vs. community based laboratories)? Patient subgroups within the Medicare beneficiary population (e.g., age)? 5. Please identify and discuss any evidence gaps in assessing outcomes of interest to CMS for both DNA- or RNA-based testing to predict tissue of origin for CUP, and FISH testing for cervical cancer/pre-cancer in patients with ASCUS/LSIL. 6. Please comment on whether CMS should encourage development of additional evidence relevant to coverage determinations for DNA- or RNA-based testing to predict tissue of origin for CUP, and FISH testing for cervical cancer/pre-cancer in patients with ASCUS/LSIL. Download scoresheet . Roster: Rita Redberg, MD, MS Chair Professor of Medicine UCSF School of Medicine Division of Cardiology University of California, San Francisco Medical Center Art Sedrakyan, MD, PhD Vice Chair Associate Professor and Director Patient Centered Comparative Outcomes Research Program Weill Cornell Medical School David C. Beyer, MD, FACR Vice President Radiation Oncologist Arizona Oncology Services, Inc. Scottsdale Radiation Oncology Mary A. Blegen, RN, PhD, FAAN Professor Emerita University of California, San Francisco Steven Gutman, MD Strategic Advisor Myraqa Inc. David Howard, PhD Associate Professor Department of Health Policy and Management Emory University Pamela R. Massey, Pt, MS Physical Therapist Jan Nowak, PhD, MD Clinical Assistant Professor of Pathology Department of Pathology and Laboratory Medicine NorthShore University HealthSystem University of Chicago James Rizzo, MD, MS Associate Scientific Director Professor of Medicine Bone Marrow Transplantation Program Division of Hematology and Oncology Department of Medicine Center for International Blood and Marrow Transplant Research (CIBMTR) Medical College of Wisconsin Amy E. Sanders, MD, MS Assistant Professor Department of Neurology/Einstein Aging Study Albert Einstein College of Medicine A. Oliver Sartor, MD Medical Director Tulane Cancer Center C.E. Bernadine Laborde Professor of Cancer Research Departments of Medicine and Urology Tulane Medical School Eric C. Stecker, MD Assistant Professor of Medicine Cardiovascular Medicine and Electrophysiology Director CCU and Inpatient Cardiology Services Division of Cardiovascular Medicine Oregon Health and Science University Sandra L. Wong, MD, MS Department of Surgery Division of Surgical Oncology University of Michigan Medical School Industry Representative Martin D. Marciniak, MPP, PhD Vice President US Health Outcomes GlaxoSmithKline Guest Panel Members Barbara Conley, MD Associate Director Cancer Diagnosis Program Division of Cancer Treatment and Diagnosis National Cancer Institute National Institute of Health Dorothy L. Rosenthal, MD, FIAC Professor of Pathology, Oncology and Gynecology/Obstetrics Johns Hopkins School of Medicine Invited Guest Speakers Barbara Conley, MD Associate Director Cancer Diagnosis Program Division of Cancer Treatment and Diagnosis National Cancer Institute National Institute of Health Sreelatha Meleth, PhD Senior Research Statistician Social Statistical and Environmental Sciences RTI International Dorothy L. Rosenthal, MD, FIAC Professor of Pathology, Oncology and Gynecology/Obstetrics Johns Hopkins School of Medicine Katrin Uhlig, MD, MS Attending Physician Division of Nephrology Tufts Medical Center Associate Professor Tufts University School of Medicine Nedra Whitehead, PhD, MS, CGC Senior Genetic Epidemiologist Statistics and Epidemiology RTI International CMS Liaison James Rollins, MD, PhD Director Division of Items and Devices Coverage and Analysis Group Executive Secretary Maria Ellis Coverage and Analysis Group Speakers List: Medicare Evidence Development & Coverage Advisory Committee May 1, 2013 SPEAKER LIST *6 MINUTES PER SPEAKER* E. Robert Wassman, MD, FAAP, FACMG , Chief Medical Officer, Rosetta Genomics Margaret Havens Neal, MD, FCAP , Pathologist with KWB Pathology Associates, Tallahassee FL, Member, Economic Affairs Committee, College of American Pathologists Bernard H. Berins - No Powerpoint Presentation F. Anthony Greco, MD , Sarah Cannon Cancer Center and Research Institute Lawrence M. Weiss, MD , Chairman Emeritus, Department of Pathology, City of Hope National Medical Center, Senior Consultative Pathologist, Clarient, Inc. Catherine Schnabel, MD , Vice President, Medical, Clinical & Regulatory Affairs, bioTheranostics, Inc.