Update from the 2011 symposium: MOH testing criteria

Size: px

Start display at page:

Download "Update from the 2011 symposium: MOH testing criteria"

Jason McCormick
5 years ago
Views:

1 Update from the 2011 symposium: MOH testing criteria Melyssa Aronson, MS, (C)CGC Zane Cohen Centre for Digestive Disease May 26, 2017

2 Criteria Working Group 2011 Symposium Concerns expressed: Last revised in 2005 Very colorectal-centric. Extracolonic FAP and LS? Very strict no 10% category or unaffected Isolated cancer had to be under age 35 Tedious to count up polyps for polyposis Should MAP be lumped into criteria with FAP/AFAP? 2

3 Timeline (exceedingly slow ) June 2011 Symposium December 2011 CCO GI Site Group Melyssa Aronson, Eva Tomiak, Blaise Clarke November 2012 Molecular Oncology Advisory Committee (MOAC) Hereditary Cancer Screening Sub-Committee (HCSSC) Lynch Syndrome Working Group (chaired by Aaron Pollett) Evidence Summary document on IHC/MSI/BRAF/Methylation 3

4 September

5 Hereditary CRC working group: Melyssa Aronson (lead), Eva Tomiak, Cathy Gilpin, Tracy Graham, Kevin Zbuk, Heather Dorman Objective Development of an advice document (position statement or recommendation report) which will offer current evidence-based criteria for eligibility for testing for the presence of mutations for hereditary GI cancer syndromes and associated cancers. Approach Jurisdictional/environmental scan of clinical testing criteria Survey to all GI cancer genetics programs to solicit specific and structured input Review of existing literature and consensus documents 5

6 CCO literature reviews ( ) performed by: Jennifer Guo, Dana Wilson-Li, Jennifer Hart 1. Sensitivity and specificity of Amsterdam I/II, and revised Bethesda Guidelines 2. a. Performance MMRpro, PREMM1,2,6, & MMRpredict b. Characteristics of mutation carriers missed by prediction models 3. Frequency of LS in extracolonic tumours 4. Current clinical criteria for FAP, AFAP, and MAP 5. Frequency of FAP/MAP in extracolonic tumours 6

7 7

8 Timeline (exceedingly slow ) February 2016 Literature review complete. Began assess criteria April 2016 Criteria revised and finalized by working group Sent out to MOAC and other stakeholders for feedback June 2016 Incorporated feedback and finalized criteria May 2017 Revised criteria approved by Clinical Programs and Quality Initiatives (Dr. Robin McLeod), CCO Submitted to MOH on May 25,

9 Revised Lynch Syndrome and FAP/MAP Testing Criteria (2016) A. Lynch syndrome Known MMR pathogenic variant. Amsterdam I/II criteria family must meet all of the following criteria: 9

10 Colorectal cancer Personal history of COLORECTAL cancer with any of the following: Diagnosed under age 35. PLUS any second primary Lynch syndrome cancer (one diagnosed under 60). Diagnosed under age 50 with a first or second-degree relative with any Lynch syndrome cancer under age 50. PLUS two relatives with any Lynch syndrome cancer. One diagnosis should be under age 50. Two of the three family members must be in a first-degree relationship. 10

11 Endometrial cancer Personal history of ENDOMETRIAL cancer with any of the following: Diagnosed under age 35. PLUS any second primary colorectal cancer, one diagnosed under age 60. Diagnosed at any age PLUS a second primary Ca + (refer to Lynch syndrome cancer definitions #d) (Note: For synchronous ovarian and endometrial cancer, every effort should be made to confirm they are separate primary cancers.) Diagnosed under age 55 with a first or second-degree relative with colorectal cancer under age 50, or a Ca + or sebaceous neoplasm under age 55. PLUS two relatives with any Lynch syndrome cancer. One diagnosis should be under age 50. Two of the three family members 11 must be in a first-degree relationship.

12 LS-related cancer Personal history of a Ca + (small bowel, gastric, gastroesophageal (GE) junction, hepatobiliary, ovarian (excluding borderline histology), ureter, transitional cell kidney cancer (urothelial), glioblastoma) with any of the following: Diagnosed under age 35. PLUS two relatives with any Lynch syndrome cancer. One diagnosis should be under age 50. Two of the three family members must be in a first-degree relationship. *See above for criteria on Ca + plus endometrial or colorectal cancer in family history or self. 12

13 Sebaceous neoplasm a) Personal history of an isolated SEBACEOUS NEOPLASM, PLUS 2 of the following criteria: Diagnosed under age 60. Personal history of any Lynch syndrome cancer. First or second degree relative with any Lynch syndrome cancer. OR b) Personal history of two or more SEBACEOUS NEOPLASMS. 13

14 IHC deficient cases Personal history of IMMUNODEFICIENT tumour as follows: MSH2, MSH6 and PMS2 deficient tumour (any age). MLH1 deficient tumour in individuals < age 60. MLH1 deficient tumour in individual 60 with no promoter MLH1 methylation or BRAF mutation. (NOTE: IHC, MLH1 methylation and BRAF testing would need to be done by a referring pathology laboratory PRIOR to genetic referral if individual meets no other criteria). 14

15 Unaffected and 10% rule a) Affected and unaffected individuals with a 10% probability of carrying an MMR pathogenic variant, using one of the following mutation prediction models: MMRpro, PREMM(1,2,6) or other validated risk models. OR b) Exceptional cases that do not meet #8a, but likely has a 10% probability of carrying an MMR pathogenic variant by clinical judgment. Every effort should be made to do tumour screening (i.e. IHC) on an affected individual (deceased or living) prior to offering germline testing. Germline testing should not be offered, if tumour screening is negative. 15

Adenomatous Polyposis Testing (FAP and MAP) 1. Known APC or MUTYH pathogenic variant. 2. Individuals with > 20 adenomatous polyps, regardless of age. 3.

16 Adenomatous Polyposis Testing (FAP and MAP) 1. Known APC or MUTYH pathogenic variant. 2. Individuals with > 20 adenomatous polyps, regardless of age. 3. Individuals with the following isolated extracolonic tumour, regardless of personal and family history, as follows: cribriform-morular variant (cmv) of papillary thyroid cancer or hepatoblastoma 4. Individual with > 10 adenomas PLUS one of the following criteria: Age of onset <40 years of age; OR first or second degree relative with > 10 adenomas or colorectal cancer under 50 years of age; or serrated polyposis*; or an extracolonic feature, including desmoid, multifocal or bilateral chrpe, osteoma, gardner-type fibroma, papillary thyroid cancer, hepatoblastoma, and small bowel cancer 5. A pedigree strongly suggestive of hereditary FAP and MAP (i.e. the risk of carrying a mutation for the individual being tested is higher than 10%). 16

17 Why bother with clinical criteria? 1. Reflex IHC will not capture all patients a. Prior to population testing/not at all hospitals b. Patients tested outside of Ontario c. Unaffected individuals 2. Guidance on which IHC results to work-up 3. Equitable care across the province 17

18 Data from the 2017 Hereditary GI Cancer Symposium Survey Strongly Agree Agree Neutral Disagree Strongly Disagree 18

19 Data from the 2017 Hereditary GI Cancer Symposium Survey 50% of clinics test individuals outside of the MOH criteria 3 clinics report using models for unaffected risk 1 clinic uses NCCN Discretion (ie. Adoption, small families) Table: Non-MOH criteria currently being used in Ontario CRC 9 clinics 6 clinics <50 <60 Other comments Endometrial 6 clinics 2 clinics 1 clinic: case-by-case LS-related 4 clinics 1 clinic 1 clinic: ovarian 1 clinic: all sebaceous neoplasm 19

20 20

The Genetics of Familial Polyposis

The Genetics of Familial Polyposis Thursday, September 24 th 2015 Kara Semotiuk, MS, (C)CGC & Laura Winter, MSc, CGC Genetic Counsellors at the FGICR Familial Polyposis Familial Can run in the family related