Super early cancer screening for the ultra rich Asian
•
1 like•395 views
This presentation talks about the nonconventional ways to look for cancer. It discusses next generation sequencing for multilane panels for cancer predisposition syndromes, whole genome sequencing, circulating tumor cells, circulating tumor DNA, and CancerSEEK. It also discusses the traditional cancer screening guidelines by the American Cancer Society and the USPSTF.
Recommended
More Related Content
What's hot
What's hot (20)
Similar to Super early cancer screening for the ultra rich Asian
Similar to Super early cancer screening for the ultra rich Asian (20)
More from Mary Ondinee Manalo Igot
More from Mary Ondinee Manalo Igot (20)
Recently uploaded
Recently uploaded (20)
Super early cancer screening for the ultra rich Asian
- 1. (Not) DYING YOUNG: SUPER Early Cancer Detection for the CRAZY RICH ASIAN Mary Ondinee Manalo - Igot, MD Medical Oncologist / Neuro – Oncologist
- 2. Astrid Teo (née Leong): “Doctor, I want you to look for cancer in my body lah. Please do EVERYTHING so I won’t die from cancer. ”
- 3. Astrid Teo (née Leong): “Doctor, I want you to look for cancer in my body lah. Please do EVERYTHING so I won’t die from cancer. ” The Worried Well Patient “My body deserves at least the same level of attention as my cars. Run the necessary tests to keep it in a good working condition.
- 4. Objectives 1. Present other options for early detection of cancer 2. Discuss their advantages and disadvantages 3. Review the 2019 “traditional” cancer screening guidelines
- 5. Super EARLY cancer detection Gene panels or whole genome sequencing by Next Generation Sequencing No cancer yet but will / might develop cancer Beginning or Low Volume Cancer Circulating tumor cells (CTC) Liquid biopsy Circulating tumor DNA (ctDNA) CancerSEEK EARLY CANCER DETECTION 2019 GUIDELINES FOR CANCER SCREENING THE CASE FOR PET CT SCAN CONCLUSION
- 6. Super EARLY cancer detection Gene panels or whole genome sequencing by Next Generation Sequencing No cancer yet but will / might develop cancer Beginning or Low Volume Cancer Circulating tumor cells (CTC) Liquid biopsy Circulating tumor DNA (ctDNA) CancerSEEK EARLY CANCER DETECTION 2019 GUIDELINES FOR CANCER SCREENING THE CASE FOR PET CT SCAN CONCLUSION
- 7. “All cancer is genetic, but not all cancer is hereditary.” EARLY CANCER DETECTION 2019 GUIDELINES FOR CANCER SCREENING THE CASE FOR PET CT SCAN CONCLUSION
- 8. Types of Cancer Mutations • GERMLINE CANCER MUTATIONS • mutations that are present in every cell, either because they have been inherited or occur at conception • “cancer predisposition genes (CPGs)” • 114 cancer predisposition genes discovered • SOMATIC CANCER MUTATIONS • Oncogenic mutations that occur after birth, within a specific cell • Hallmark of cancer • 468 somatic driver mutations, of which 49 are also included in the cancer predisposition genes EARLY CANCER DETECTION 2019 GUIDELINES FOR CANCER SCREENING THE CASE FOR PET CT SCAN CONCLUSION Rahman, Clinical Medicine 2014 Vol 14, No 4:436-9
- 9. Multigene panels for cancer predisposition genes
- 10. Cancer predisposition genes (CPGs) • Germline mutations that cause hereditary cancer syndromes • Unique in that they can serve as a biomarker for future disease • Examples: Hereditary breast cancer and ovarian cancer syndrome - Genes: BRCA 1 and BRCA 1 - Related cancer types: Female breast, ovarian, prostate, pancreatic and male breast cancer Li-Fraumeni syndrome - Gene: TP53 - Related cancer types: breast cancer, soft tissue sarcoma, osteosarcoma, brain tumors, adrenocortical cancer, and others EARLY CANCER DETECTION 2019 GUIDELINES FOR CANCER SCREENING THE CASE FOR PET CT SCAN CONCLUSION Rahman, Clinical Medicine 2014 Vol 14, No 4:436-9
- 11. Cancer predisposition genes (CPGs) • CPG mutation carriers are at increased risk to develop one or more cancers in their lifetime • More radical surgery might be appropriate • Radiation treatment or chemotherapy might be modified • Can provide prognostic information and tailored surveillance • Risk reducing interventions are available • As per guidelines, screening with CPGs should be offered to a person who: 1. has a personal history consistent with a cancer predisposition syndrome 2. if he/she has a first-, second-, or a third-degree blood relative who was diagnosed with a cancer predisposition syndrome. EARLY CANCER DETECTION 2019 GUIDELINES FOR CANCER SCREENING THE CASE FOR PET CT SCAN CONCLUSION Rahman, Clinical Medicine 2014 Vol 14, No 4:436-9
- 12. Cancer predisposition genes (CPGs) as a tool for EARLY DETECTION of cancer on healthy individuals with no family history of cancer is presently being studied. • This MIGHT be the future of early cancer detection in the next few years. • Drawbacks: • Less likely that you have a faulty gene • The tests cannot guarantee whether you will develop cancer if positive • If negative, the test does not exempt you from a cancer due to a somatic mutation or from a germline mutation that has not yet been discovered. EARLY CANCER DETECTION 2019 GUIDELINES FOR CANCER SCREENING THE CASE FOR PET CT SCAN CONCLUSION Rahman, Clinical Medicine 2014 Vol 14, No 4:436-9
- 13. EARLY CANCER DETECTION 2019 GUIDELINES FOR CANCER SCREENING THE CASE FOR PET CT SCAN CONCLUSION • DNA sequencing technology has evolved rapidly over the recent years. • Traditionally, gene testing relied on development of individual tests for each CPG using costly and time-consuming methods. Price et al. Biological Res for Nursing 2018, Vol 20(2) 192-204.
- 14. The secret of Next Generation Sequencing is AUTOMATION. EARLY CANCER DETECTION 2019 GUIDELINES FOR CANCER SCREENING THE CASE FOR PET CT SCAN CONCLUSION Rahman, Clinical Medicine 2014 Vol 14, No 4:436-9
- 15. EARLY CANCER DETECTION 2019 GUIDELINES FOR CANCER SCREENING THE CASE FOR PET CT SCAN CONCLUSION
- 16. Increasing CPG testing • The laborious, expensive nature of gene testing previously meant that: • (i) strict eligibility criteria to limit testing were required, and • (ii) testing infrastructure was developed primarily to serve the complex needs of unaffected individuals who had time to wait for the results. • Faster, more affordable testing now enables eligibility criteria to be relaxed and for results to be delivered within the time frame required to impact cancer management. EARLY CANCER DETECTION 2019 GUIDELINES FOR CANCER SCREENING THE CASE FOR PET CT SCAN CONCLUSION Rahman, Clinical Medicine 2014 Vol 14, No 4:436-9
- 17. EARLY CANCER DETECTION 2019 GUIDELINES FOR CANCER SCREENING THE CASE FOR PET CT SCAN CONCLUSION ASIAN HOSPITAL & MEDICAL CENTER In partnership with Ambry Genetics (California, USA) CANCER PREDISPOSITION MULTIGENE PANELS CancerNext® CustomNext-Cancer® BreastNext® OvaNext® ProstateNext® ColoNext® BRCAplus® TumorNext-HRD™ TumorNext-Lynch™ Result TAT: 3-4 weeks https://www.ambrygen.com/clinician/oncology/test-menu Slides lifted from the presentation of Ms Maya Montemayor of the Pathology Department
- 18. EARLY CANCER DETECTION 2019 GUIDELINES FOR CANCER SCREENING THE CASE FOR PET CT SCAN CONCLUSION ASIAN HOSPITAL & MEDICAL CENTER In partnership with Ambry Genetics (California, USA) CancerNext® = PhP 111,642.34 (± Php 5-10,000) A comprehensive 34-gene panel that identifies inherited risks for at least 8 types of cancers (breast, lung, colorectal, ovarian, uterine, and others) to give information for better treatment and management decisions. CustomNext-Cancer® = PhP 142,705.20 (± Php 5-10,000) For patients with a complex or family history of cancer; with the flexibility to choose which genes to analyze for accurate diagnosis, treatment and management of your patient’s cancer risks. https://www.ambrygen.com/clinician/oncology/test-menu Slides lifted from the presentation of Ms Maya Montemayor of the Pathology Department
- 19. EARLY CANCER DETECTION 2019 GUIDELINES FOR CANCER SCREENING THE CASE FOR PET CT SCAN CONCLUSION ASIAN HOSPITAL & MEDICAL CENTER In partnership with Ambry Genetics (California, USA) BreastNext® = PhP 103,876.33 (± Php 5-10,000) For understanding high-risk breast cancer patients; those with early-onset or multiple diagnoses of breast cancer, male breast cancer and/or with a family history of disease. A 17-gene panel that offers more precision to identify and manage hereditary breast cancer. BRCAplus® = P96,110.91 (± Php 5-10,000) A genetic test designed specifically for patients with high risk personal and/or family breast cancer history. BRCAplus tests critical breast cancer genes with published guidelines for medical management, to help patients make confident, personalized screening and prevention decisions. https://www.ambrygen.com/clinician/oncology/test-menu Slides lifted from the presentation of Ms Maya Montemayor of the Pathology Department
- 20. EARLY CANCER DETECTION 2019 GUIDELINES FOR CANCER SCREENING THE CASE FOR PET CT SCAN CONCLUSION ASIAN HOSPITAL & MEDICAL CENTER In partnership with Ambry Genetics (California, USA) OvaNext® = Php 107,759.49 (± Php 5-10,000) A 25-genetic panel that offers the most comprehensive testing for gynecologic cancers to increase the chance of identifying and managing hereditary cancer risks. ProstateNext® = PhP 96,110.91 (± Php 5-10,000) A 14-gene panel that offers more precision to identify and manage hereditary prostate cancer, since hereditary prostate cancer is not well understood or recognized, to provide clinicians clear results and guide them in their treatment decisions. https://www.ambrygen.com/clinician/oncology/test-menu Slides lifted from the presentation of Ms Maya Montemayor of the Pathology Department
- 21. EARLY CANCER DETECTION 2019 GUIDELINES FOR CANCER SCREENING THE CASE FOR PET CT SCAN CONCLUSION ASIAN HOSPITAL & MEDICAL CENTER In partnership with Ambry Genetics (California, USA) ColoNext® = PhP 103, 876.63 A 17-gene panel designed to provide more precise data to help guide personalized medical management recommendations such as earlier or more frequent colonoscopies. TumorNext-Lynch® = PhP 157,460.06 A test that gives the most comprehensive and accurate information when the need to rule out or confirm Lynch Syndrome or to determine if your patient can start PD-L1 or PD-1 immunotherapy. It is a single test that looks at both tumor and germline mutations, giving clearer information to better guide treatment decisions. https://www.ambrygen.com/clinician/oncology/test-menu Slides lifted from the presentation of Ms Maya Montemayor of the Pathology Department
- 23. Whole Genome Sequencing • Gene panels of 5-100 CPGs are the ones more readily available. In time, it is likely that these will be superseded by whole-genome sequencing, which would also enable genetic information about other medical conditions or drug responses to be harvested. • Uses the high thouroughput next generation sequencing technology • Risk for other diseases can also be determined using this EARLY CANCER DETECTION 2019 GUIDELINES FOR CANCER SCREENING THE CASE FOR PET CT SCAN CONCLUSION
- 24. EARLY CANCER DETECTION 2019 GUIDELINES FOR CANCER SCREENING THE CASE FOR PET CT SCAN CONCLUSION ASIAN HOSPITAL & MEDICAL CENTER In partnership with Ambry Genetics (California, USA) WHOLE GENOME SEQUENCING ExomeNext Proband® = PhP 375,676.63 (± Php 5- 10,000.00) - is a comprehensive test analyzing all 20,000 genes of the human genome, providing detailed information on novel discoveries to improve patient outcomes. This test is indicated when: 1. Prior testing has been negative and has not identified a genetic explanation 2. No testing available; limited or no comprehensive tests available for the patient’s condition 3. Unclear differential diagnosis: clinical presentation does not correspond with a known genetic disorder or multiple genes may be involved. Result TAT: 4 weeks https://www.ambrygen.com/clinician/oncology/test-menu Slides lifted from the presentation of Ms Maya Montemayor of the Pathology Department
- 25. Advantages 1) Just a blood exam 2) Faster turnaround time because of next generation sequencing Disadvantages 1) No large scale studies on healthy controls 2) Diagnostic sensitivity is an issue depending on the machine used 3) Failure to identify the underlying tissue of origin 4) Very expensive EARLY CANCER DETECTION 2019 GUIDELINES FOR CANCER SCREENING THE CASE FOR PET CT SCAN CONCLUSION Multigene Testing for Cancer Predisposition Genes and Whole Genome Testing for Early Cancer Detection
- 26. Super EARLY cancer detection Gene panels or whole genome sequencing by Next Generation Sequencing No cancer yet but will / might develop cancer Beginning or Low Volume Cancer Circulating tumor cells (CTC) Liquid biopsy Circulating tumor DNA (ctDNA) CancerSEEK EARLY CANCER DETECTION 2019 GUIDELINES FOR CANCER SCREENING THE CASE FOR PET CT SCAN CONCLUSION
- 27. Super EARLY cancer detection Gene panels or whole genome sequencing by Next Generation Sequencing No cancer yet but will / might develop cancer Beginning or Low Volume Cancer Circulating tumor cells (CTC) Liquid biopsy Circulating tumor DNA (ctDNA) CancerSEEK EARLY CANCER DETECTION 2019 GUIDELINES FOR CANCER SCREENING THE CASE FOR PET CT SCAN CONCLUSION
- 28. EARLY CANCER DETECTION 2019 GUIDELINES FOR CANCER SCREENING THE CASE FOR PET CT SCAN CONCLUSION
- 29. Super EARLY cancer detection Gene panels or whole genome sequencing by Next Generation Sequencing No cancer yet but will / might develop cancer Beginning or Low Volume Cancer Circulating tumor cells (CTC) Liquid biopsy Circulating tumor DNA (ctDNA) CancerSEEK EARLY CANCER DETECTION 2019 GUIDELINES FOR CANCER SCREENING THE CASE FOR PET CT SCAN CONCLUSION
- 30. Circulating Tumor Cells (CTCs)
- 31. Circulating Tumor Cells (CTCs) • Cancer cells that detach from their primary site during the process of cancer metastases • If present, can be isolated and characterized and may serve as a liquid biopsy for cancer patients • First reported by Ashworth since 1869 • BUT!!!! CTCs are RARE EVENTS (AND NOT ALWAYS PRESENT) compared to the number of hematopoietic cells, therefore, their detection and enumeration is challenging. EARLY CANCER DETECTION 2019 GUIDELINES FOR CANCER SCREENING THE CASE FOR PET CT SCAN CONCLUSION Andree et al. Challenges in circulating tumor cell detection by the CellSearch system. Molecular Oncology 10 (2016) 395-407
- 32. Immunocytochemistry. Typical images of CTC immuno-magnetically enriched using EpCAM labeled ferrofluids and stained by immunocytochemistry with hematoxylin nuclear stain (blue purple) and cytokeratin (red). The brown yellow color can be contributed to the ferrofluids that are approximately 175 nm in size and is visual due to the accumulation. EARLY CANCER DETECTION 2019 GUIDELINES FOR CANCER SCREENING THE CASE FOR PET CT SCAN CONCLUSION Andree et al. Challenges in circulating tumor cell detection by the CellSearch system. Molecular Oncology 10 (2016) 395-407
- 33. CellSearch EARLY CANCER DETECTION 2019 GUIDELINES FOR CANCER SCREENING THE CASE FOR PET CT SCAN CONCLUSION • The first and only clinically validated method for CTC detection that has been cleared by the U.S. FDA • Developed by the Veridex Division of Johnson and Johnson
- 34. CellSearch EARLY CANCER DETECTION 2019 GUIDELINES FOR CANCER SCREENING THE CASE FOR PET CT SCAN CONCLUSION • Labels tumor cells with epithelial cell adhesion molecule (EpCAM) and cytokeratin (CK). • White blood cells are labelled with anti- CD45, so they are selected out. Andree et al. Challenges in circulating tumor cell detection by the CellSearch system. Molecular Oncology 10 (2016) 395-407
- 35. EARLY CANCER DETECTION 2019 GUIDELINES FOR CANCER SCREENING THE CASE FOR PET CT SCAN CONCLUSION CellSearch • The only validated method for CTC detection that has been cleared by the U.S. FDA • Labels tumor cells with epithelial cell adhesion molecule (EpCAM)
- 36. Circulating Tumor Cells (CTCs) via CellSearch ADVANTAGES • Just a blood test • If positive, means you really have cancer EARLY CANCER DETECTION 2019 GUIDELINES FOR CANCER SCREENING THE CASE FOR PET CT SCAN CONCLUSION DISADVANTAGES • Fails to identify histology/cytology >98% of the time • Fails to identify the tissue or organ of origin • Only CARCINOMAS have been validated to be identified with accuracy • “melanoma kits”, “endothelial kits” have been developed • Once collected in special tubes, specimens have to be processed in 72 hours • Temperature and movement labile • Expensive Andree et al. Challenges in circulating tumor cell detection by the CellSearch system. Molecular Oncology 10 (2016) 395-407
- 37. EARLY CANCER DETECTION 2019 GUIDELINES FOR CANCER SCREENING THE CASE FOR PET CT SCAN CONCLUSION ASIAN HOSPITAL & MEDICAL CENTER https://www.ambrygen.com/clinician/oncology/test-menu Slides lifted from the presentation of Ms Maya Montemayor of the Pathology Department • Not available at the moment at our hospital • If will be done elsewhere, around PhP 100,000 • My thoughts on CTCs: • Circulating tumor cells are very hard to handle • The machine has to be in your hospital to decrease apoptosis • Specimens have to be run within 3 days • Unless the tumor burden is very heavy, most will turn out to be negative = POOR SENSITIVITY, POOR SPECIFICITY re TISSUE of ORIGIN • Best for metastatic tumors where: 1. the histology is known already 2. you want to monitor response to treatment (i.e. decrease/increase in CTCs in peripheral blood)
- 38. Circulating tumor DNA (ctDNA)
- 39. Circulating Tumor DNA (ctDNA) • Elevated concentrations of cell-free ctDNA fragments have been found in blood plasma and serum of cancer patients. • ctDNA originate from APOPTOTIC or NECROTIC tumor cells which discharge DNA into the circulation EARLY CANCER DETECTION 2019 GUIDELINES FOR CANCER SCREENING THE CASE FOR PET CT SCAN CONCLUSION Dawson et al. Analysis of circulating tumor DNA to monitor metastatic disease. NEJM 2013; 368:1199-209 Alix-Panabieres, Annals of Translational Medicine 2013; 1(2):18
- 40. EARLY CANCER DETECTION 2019 GUIDELINES FOR CANCER SCREENING THE CASE FOR PET CT SCAN CONCLUSION Dawson et al. Analysis of circulating tumor DNA to monitor metastatic disease. NEJM 2013; 368:1199-209 Alix-Panabieres, Annals of Translational Medicine 2013; 1(2):18 PROOF OF PRINCIPLE paper for METASTATIC cancers
- 41. EARLY CANCER DETECTION 2019 GUIDELINES FOR CANCER SCREENING THE CASE FOR PET CT SCAN CONCLUSION Bettegowda et al. Detection of circulating tumor DNA in early- and late-stage human malignancies. Sci Transl Med 6(2014 Feb 19) 224ra24. PROOF OF PRINCIPLE paper for EARLY cancers
- 42. Circulating Tumor DNA (ctDNA) • Proof of principle paper indicates that presence of ctDNA in pre-symptomatic individuals MIGHT become a useful screening strategy to complement more traditional, but often more invasive approaches, such as mammography and colonoscopy. • Considerable challenges: • Amount of circulating tumor DNA is limited (around 5-10 ng/mL of plasma or LESS in early disease) • Most ctDNA released by apoptosisis highly degraded • Cell lysis must be avoided at any cost to prevent the release of normal DNA EARLY CANCER DETECTION 2019 GUIDELINES FOR CANCER SCREENING THE CASE FOR PET CT SCAN CONCLUSION Nikolaev et al. ctDNA: Preanalytical validation and quality control in a diagnostic laboratory. Analytical biochemistry 542 (2018)34-39.
- 43. EARLY CANCER DETECTION 2019 GUIDELINES FOR CANCER SCREENING THE CASE FOR PET CT SCAN CONCLUSION
- 44. Circulating tumor DNA (ctDNA) ADVANTAGES • Just a blood test • Less labile to movement and heat • Provides a personalized snapshot of the disease by identifying actionable mutations EARLY CANCER DETECTION 2019 GUIDELINES FOR CANCER SCREENING THE CASE FOR PET CT SCAN CONCLUSION DISADVANTAGES • Fails to identify histology/cytology unless a particular mutation is specific to a particular organ • Fails to identify the tissue or organ of origin in some • Expensive
- 45. EARLY CANCER DETECTION 2019 GUIDELINES FOR CANCER SCREENING THE CASE FOR PET CT SCAN CONCLUSION ASIAN HOSPITAL & MEDICAL CENTER In partnership with OncoDNA Solutions (Gosselies, Belgium) https://www.ambrygen.com/clinician/oncology/test-menu Slides lifted from the presentation of Ms Maya Montemayor of the Pathology Department OncoTRACE™ = PhP 123,113.78 for any Stage IV metastatic cancer with established genomic profile (200 genes or more) Designed on the unique molecular signature of the patient’s tumor Based on circulating tumor DNA in liquid biopsies (2 blood samples) Targets more individual-specific mutations leading to a higher probability of ctDNA detection to monitor recurrence Reporting of new variant(s) associated with resistance and/or new treatment options Treatment options for targeted therapies Dynamic evolution of the personalized variants Result TAT: 3-4 weeks
- 46. EARLY CANCER DETECTION 2019 GUIDELINES FOR CANCER SCREENING THE CASE FOR PET CT SCAN CONCLUSION ASIAN HOSPITAL & MEDICAL CENTER In partnership with OncoDNA Solutions (Gosselies, Belgium) https://www.ambrygen.com/clinician/oncology/test-menu Slides lifted from the presentation of Ms Maya Montemayor of the Pathology Department OncoSELECT™ = PhP 106,588.44 for metastatic cancers of the following type: Non-Small Cell Lung Cancer Colorectal Cancer Breast Cancer (HR+/HER2+) Based on circulating tumor DNA in liquid biopsies (2 blood samples) Analysis of >100 mutations of resistance and sensitivity Tool to identify therapeutic solutions (targeted therapies) for cancer patients whose tumors are not biopsied Reporting of new variant(s) associated with resistance and/or new treatment options Treatment options for approved targeted therapies Result TAT: 3-4 weeks
- 47. CancerSEEK
- 48. Cohen et al., Science 359, 926-930 (23 February 2018) EARLY CANCER DETECTION 2019 GUIDELINES FOR CANCER SCREENING THE CASE FOR PET CT SCAN CONCLUSION SCREENS FOR 8 DIFFERENT CANCERS: 1. Ovary 2. Liver 3. Stomach 4. Pancreas 5. Esophagus 6. Colorectal 7. Lung 8. Breast Sensitivities: 69-98% Specificity: 99% “The sensitivity for Stage I liver cancer was 100%.”
- 49. EARLY CANCER DETECTION 2019 GUIDELINES FOR CANCER SCREENING THE CASE FOR PET CT SCAN CONCLUSION
- 50. EARLY CANCER DETECTION 2019 GUIDELINES FOR CANCER SCREENING THE CASE FOR PET CT SCAN CONCLUSION CancerSEEK ADVANTAGES • Just a blood test • Can identify the tissue of origin • Detects early stage cancers • Cheaper (allegedly $500) DISADVANTAGES • Screens only 8 cancers • False positives noted in inflammatory and infectious conditions • No large scale study yet on healthy control individuals • No data yet on its pick up of premalignant lesions
- 51. PET CT SCAN
- 52. PET CT Scan for Cancer Screening • Whole body scans are a poor screening tool. • Whole body scans use a lot of radiation. • Whole body scans can lead to unnecessary tests. • No medical societies recommend whole-body scans. • The utility of PET CT scan for cancer screening can only be assessed in a prospective randomized trial. EARLY CANCER DETECTION 2019 GUIDELINES FOR CANCER SCREENING THE CASE FOR PET CT SCAN CONCLUSION American Cancer Society American College of Preventive Medicine
- 53. Traditional CANCER SCREENING for the not CRAZY
- 54. Who’s Right When it Comes to Screening? EARLY CANCER DETECTION 2019 GUIDELINES FOR CANCER SCREENING THE CASE FOR PET CT SCAN CONCLUSION
- 55. EARLY CANCER DETECTION 2019 GUIDELINES FOR CANCER SCREENING THE CASE FOR PET CT SCAN CONCLUSION American Cancer Society (ACS) versus U.S. Preventive Services Task Force (USPSTF) Cancer Screening Guidelines
- 56. EARLY CANCER DETECTION 2019 GUIDELINES FOR CANCER SCREENING THE CASE FOR PET CT SCAN CONCLUSION 2019 Screening Recommendations for Breast Cancer Test or Procedure American Cancer Society U.S. Preventive Services Task Force Breast self examination No recommendation “D” Clinical examination No recommendation Women ≥40 years: “I” INSUFFICIENT EVIDENCE Mammography Women 40-44 years: Should be able to start screening if they want to yearly (“B”) Women ≥45 years: Screen annually for as long as the woman is in good health and is expected to live for 10 years or more Women ≥55 years: Can continue yearly or every 2 years Women 40–49 years: The decision should be an individual one, and take patient context/values into account (“C”) Women 50–74 years: Every 2 years (“B”) Women ≥75 years: “I”
- 57. EARLY CANCER DETECTION 2019 GUIDELINES FOR CANCER SCREENING THE CASE FOR PET CT SCAN CONCLUSION 2019 Screening Recommendations for Colorectal Cancer Test or Procedure American Cancer Society U.S. Preventive Services Task Force Stool-Based Tests Fecal occult blood testing (FOBT) Adults ≥45 years: Screen every year with high sensitivity guaiac based FOBT or fecal immunochemical test (FIT) only Adults 50–75 years: Annually, for high-sensitivity FOBT (“A”) Adults 76–85 years: “C” Adults ≥85 years: “D” Fecal immunochemical testing (FIT) Adults ≥45 years: Screen every year “I” Fecal DNA testing Adults ≥45 years: Screen, but interval uncertain “I”
- 58. EARLY CANCER DETECTION 2019 GUIDELINES FOR CANCER SCREENING THE CASE FOR PET CT SCAN CONCLUSION 2019 Screening Recommendations for Colorectal Cancer Test or Procedure American Cancer Society U.S. Preventive Services Task Force Direct Visualization Tests Colonoscopy Adults ≥45 years: Screen every 10 years Adults 50–75 years: every 10 years (“A”) Adults 76–85 years: “C” Adults ≥85 years: “D” Sigmoidoscopy Adults ≥45 years: Screen every 5 years Adults 50–75 years: Every 5 years in combination with high-sensitivity fecal occult blood testing (FOBT) every 3 years (“A”)a Adults 76–85 years: “C” Adults ≥85 years: “D” CT colonography Adults ≥45 years: Screen every 5 years “I”
- 59. EARLY CANCER DETECTION 2019 GUIDELINES FOR CANCER SCREENING THE CASE FOR PET CT SCAN CONCLUSION Which test to choose for screening? • “The ACS and USPSTF found no head-to-head studies demonstrating that any of the screening strategies are more effective than others, although the tests have varying levels of evidence supporting their effectiveness, as well as different strengths and limitations.” • “Offering choice in colorectal cancer screening strategies may increase the proportion of patients who will actually do the screening.”
- 60. EARLY CANCER DETECTION 2019 GUIDELINES FOR CANCER SCREENING THE CASE FOR PET CT SCAN CONCLUSION 2019 Screening Recommendations for Cervical Cancer Test or Procedure American Cancer Society (2012) U.S. Preventive Services Task Force Pap test (cytology) Women <21 years: No screening Women ages 21–29 years: Screen every 3 years Women 30–65 years: Acceptable approach to screen with cytology every 3 years (see HPV test) Women >65 years: No screening following adequate negative prior screening Women ages 21–65 years: Screen every 3 years (“A”) Women <21 years: “D” Women >65 years, with adequate, normal prior Pap screenings: “D” HPV test Women <30 years: Do not use HPV testing Women ages 30–65 years: Preferred approach to screen with HPV and cytology cotesting every 5 years (see Pap test) Women >65 years: No screening following adequate negative prior screening Women ages 30–65 years: Screen in combination with cytology every 5 years if woman desires to lengthen the screening interval (see Pap test) (“A”) Women <30 years: “D” Women >65 years, with adequate, normal prior Pap screenings: “D”
- 61. EARLY CANCER DETECTION 2019 GUIDELINES FOR CANCER SCREENING THE CASE FOR PET CT SCAN CONCLUSION 2019 Screening Recommendations for Cervical Cancer Woman’s Age How often should a woman have a Pap Test? <21 years old No testing needed 21-30 years old Pap test every 3 years 30-65 years old Pap test every 3 years, or Pap test and HPV cotesting every 5 years >65 years old No testing needed if no abnormal results for the past 10 years
- 62. EARLY CANCER DETECTION 2019 GUIDELINES FOR CANCER SCREENING THE CASE FOR PET CT SCAN CONCLUSION 2018 Screening Recommendations for Lung Cancer Test or Procedure American Cancer Society U.S. Preventive Services Task Force Low dose helical CT scan Current or former smokers aged 55-74 years in good health: Screen every year Adults aged 55-80 years with a history of smoking: Screen every year, “B” • Screening should be discontinued once: • a person has not smoked for 15 years, or • develops a health problem that substantially limits life expectancy or the ability or willingness to have curative lung surgery
- 63. EARLY CANCER DETECTION 2019 GUIDELINES FOR CANCER SCREENING THE CASE FOR PET CT SCAN CONCLUSION 2018 Screening Recommendations for Prostate Cancer Test or Procedure American Cancer Society U.S. Preventive Services Task Force Prostate Specific Antigen (PSA) Men ≥50 years: should talk to a doctor about the pros and cons of testing so they can decide if testing is the right choice for them. Men ≥45 years: should talk to a doctor about the pros and cons of testing if African American or have a father or brother who had prostate cancer before age 65. How often they are tested will depend on their PSA level. Men 55-69 years: make an individual decision about whether to be screened after a conversation with their clinician about potential benefits and harm “C” Men ≥70 years: recommends against PSA testing “D” Digital rectal examination As for PSA; if men decide to be tested, they should have the PSA blood test with or without a rectal exam. No individual recommendation
- 64. Ways to look for cancer: MOLECULAR • Multi-gene panels for cancer predisposition genes (hereditary cancer) • Whole genome sequencing • Circulating tumor cells • Circulating tumor DNA *With the help of a genetic counselor and a medical oncologist SCREENING • Breast: mammogram • Cervical: conventional / liquid based papsmear • Colorectal: stool-based assays / imaging / endoscopy • Lung: low dose chest CT • Prostate: PSA EARLY CANCER DETECTION 2019 GUIDELINES FOR CANCER SCREENING THE CASE FOR PET CT SCAN CONCLUSION
- 65. These are all happening in our hospital TODAY. Slides uploaded in https://www.slideshare.net/MaryOndineeManalo EARLY CANCER DETECTION 2019 GUIDELINES FOR CANCER SCREENING THE CASE FOR PET CT SCAN CONCLUSION
Editor's Notes
- I am Mary Ondinee Manalo – Igot, medical oncologist at the Asian Cancer Institute. This is a particularly hard topic for me especially since even for cancer screening, various medical societies have their own recommendations. I will be discussing what more we can offer a CRAZY and RICH patient.
- Astrid Teo, one of main characters in the movie Crazy Rich Asians, comes to you. She is 25/F, quite fit with no vices, no family history of cancer. She says “Doctor, I want you to look for cancer in my body lah. Please do EVERYTHING POSSIBLE so I don’t die from cancer.
- She is who we call as the WORRIED WELL PATIENT. Since she is just 25, she only falls under the cervical screening category which starts at 21 years. Will you send her home? Because in reality, cancer screening starts a bit late, so it misses a lot of cancers in the working population. I have a lot of triple negative breast cancers, gastric, brain and colorectal cancers who are just in their 20-30s (in the prime of their lives) and most of them are in their advanced stages already.
- I will divide my discussion in those who have no cancer yet but will or might develop cancer because of a hereditary or germline mutation, and those who already have beginning or VERY LOW volume of cancer too small to be detected by conventional methods or are asymptomatic.
- Under this category will be gene panels or whole genome sequencing. I would just like to point out that these panels or sequencing should be ordered by a trained practitioner (preferably a genetic counsellor) who have discussed the pros and cons of gene testing.
- It has been said that all cancer is genetic, but not all cancer is hereditary. Some studies say that hereditary cancers account for 10-30% of all the cancers out there.
- So that we wont be confused, lets define germline vs somatic mutations Germline mutations are inherited from a person’s parent. These mutations are present in every cell of the body and can be identified with a blood or buccal sample. Genes in which germline mutations lead to increased risk of cancer are called “cancer predisposition genes.” On the other hand, somatic mutations occur after birth, within a specific cell, and is present just on the tumor cell. Majority of cancers belong in this somatic mutation category.
- First we discuss multigene panels for cancer predisposition genes.
- What is a cancer predisposition gene? These are germline mutations that cause hereditary cancer. An example of a CPG will be BRCA 1 and BRCA 2 causing the hereditary breast cancer and ovarian cancer syndrome. A mutation is related with an increase in the risk of developing breast, ovarian, prostate and pancreatic cancer.
- CPG mutation carriers are at increased risk to develop one or more cancers in their life and they need more frequent monitoring and more radical treatments. As per guidelines, screening with CPGs should be offered to a person who has a personal history consistent with a cancer predisposition syndrome or has a close relative who was diagnosed with a cancer predisposition syndrome. Why only them? When these guidelines were made, gene sequencing was a new development and was very hard to do and was very very expensive. Also, without fulfilling these criteria, your risk for a hereditary cancer is LOW. BUT NOT ZERO!
- Presently, testing for CPGs as a tool for the early detection of cancer is being studied. This might actually be the future of early cancer detection in the next few years. However, taking these tests should always be under the guidance of team trained in Genetics. Why? Even if test positive, these can never determine that you will really develop cancer. And if the test is negative, the test does not exempt you from a cancer due to a somatic mutation.
- How do we do gene sequencing now? This technology has rapidly evolved over the recent years. The previous standard which is Sanger sequencing, one molecule is sequenced at a time. One molecule takes around 3 minutes to complete. But now we have high thoroughput machines that do next generation sequencing.
- The secret in next generation sequencing is automation. One can sequence millions of bases in a single run, then repeat it hundreds of times for depth and accuracy.
- Multigene testing for cancer susceptibility became commercially available since 2012. These are some of the genes which are commonly included in multigene panels. Although many laboratories now offer tests using similar NGS technologies, panel design, how genes are selected for inclusion, design of syndrome specific panels can vary between laboratories.
- The laborious and expensive nature of gene testing previously meant that: (i) strict eligibility criteria to limit testing were required. However, faster and more affordable testing now enables eligibility criteria to be relaxed and for results to be delivered within the time frame required to impact cancer management. And again, not all people are POOR. A few are extremely wealthy and I think that they deserve to at least KNOW of these technologies right now. Because if you are not in a medical field, you will not be familiar with these and as their physicians, we should offer ALL the options, SHOULD THEY ASK FOR IT.
- Asian Hospital, in partnership with Ambry Genetics has developed its molecular diagnostic division and can now test for multiple cancer predisposition genes. When requested, the results are expected within 3-4 weeks. We do not recommend a direct to consumer testing, but one has to speak first with their physician, particularly someone trained in Genetics so that the risks and benefits of genetic testing can be discussed. I was granted permission by the Pathology Head to flash the present prices.
- Prices are in ranges because they are subject to differing exchange rates and courier prices. CancerNext is available and it tests for 34-genes associated with 8 different cancers. CustomNext-Cancer is for patients with a complex family history of cancer, it gives the physician the flexibility to choose which genes to analyze.
- BreastNext is for patients who want to know their risk for a hereditary breast cancer using a 17 gene panel while BRCAplus does the same with a fewer set of genes.
- OvaNext is a 25-gene panel testing for the most common mutations in all the gynecologic cancers while ProstateNext uses 14 genes to identify your risk for prostate cancer.
- ColoNext is a 17-gene panel testing for the most common mutations in colon cancer while TumorNext Lynch will test all the mutations associated with Lynch Syndrome and an extra service of testing which drugs the patient will be sensitive too.
- Next is you have the option to sequence your whole genome.
- Since cancer panels for hereditary cancer syndromes only test for mutations specific to a syndrome, it does not exempt you from another syndrome. Whole genome sequencing takes care of this. So it basically looks for any mutation that may or may not be related to cancer. Some scientists say that this is the FUTURE of early cancer detection or cancer screening.
- Asian Hospital delivers also this service and the name of the test is ExomeNext Proband. It analyzes all the 20,000 genes of the human genome. It is quite an expensive test and you need to refer the patient to us first so we can have a genetic counsellor talk about all the intricacies of whole genome testing. This is like opening your Pandora’s Box of Hereditary Diseases so it is better to do it with guidance.
- Advantages of Gene Testing is that it just a blood exam. However, there are no large scale studies testing healthy controls. Sensitivity is an issue depending on the machine used. In the past, one laboratory wanted to patent their machine. However, the US Supreme Court ruled against it so that prices can be competitive and other labs can help out to sequence more genomes to improve efficiency and quality. However, also because of this, companies offering Next Generation Sequencing have been sprouting like mushrooms so one has to be careful on what company they choose to have their genes sequenced. Also, gene sequencing will only identify mutations, not the exact cancer that you might develop. Its also a bit expensive. Not as expensive as it once was, but still expensive. But again, going back to our theme, a few will be crazy and a few will be extremely rich.
- Next in line will be detecting cancers, the NON-TRADITIONAL WAY, for those people who are ASYMPTOMATIC but who actually have BEGINNING or LOW VOLUME CANCER ALREADY.
- We can get just a blood sample to serve as a LIQUID BIOPSY.
- In the past, imaging, solid biopsy, and protein tumor markers were the only ones available to us. Now we can look for circulating tumor cells, circulating tumor DNA, circulating RNA and tumor exosomes. For the purposes of not giving information overload, I will just be discussing …
- Circulating tumor cells and circulating tumor DNA.
- Circulating tumor cells are cancer cells that detach from their primary site during the process of metastases. If present, can be isolated and characterized and may serve as a liquid biopsy for cancer patients. It was first reported by Ashworth since 1869 and various reports have been confirming it. But there has been no technology for the past decades to isolate it with certainty and with reproducible results. Also, CTCs are RARE EVENTS and NOT ALWAYS PRESENT therefore, their detection is very challenging.
- Sometimes, if the tumor burden is REALLY VERY VERY high, you will be able to isolate this in the blood and do some staining with it. This was taken from a patient with cancer of unknown primary with tumors everywhere. However, this is not always the case. Notice also, that even if the cell looks malignant, it is hard to determine if this is carcinoma, lymphoma, sarcoma, or melanoma or just undifferentiated.
- Now comes CellSearch. It is the first and only clinically validated method for the detection of circulating tumor cells by the US FDA.
- The system was designed for the immunomagnetic enrichment, fluorescent labeling and detection of rare cell populations using just 7.5 mL of blood. There are various challenges when isolating and enumerating CTC, this system has addressed some of those by labelling white blood cells which are nearest the size to tumor cells with anti-CD45 which is the leukocyte common antigen. After that, it selects tumor cells by labelling them with cytokeratin and epithelial cell adhesion molecule.
- Once you label them, they will light up like this. These are the various appearances of circulating tumor cells in the CellSearch system. They can be just apoptotic vesicles, intact CTC, CTC clusters, or CTC/WBC clusters. Notice that when tumor cells light up like these, you just know that the patient has cancer, you will not know what type it is.
- The advantages of looking for CTCs is that it is just a blood test, if positive, it means you have cancer. However, it fails to identify the histology and the tissue of origin. Only carcinomas can be accurately be picked up, so if your patient has lymphoma or a different type of cancer, it will not be detected by the CellSearch system. Once collected the specimen has to be processed in 72 hours and it is sensitive to movement. It is also a bit expensive
- This is not available in our hospital. And for me, it is not really a loss because CTCs are very hard to handle. The machine has to be in the hospital to decrease apoptosis. The specimen has to be run in 3 days. Unless the tumor burden is very high, your sample might turn out negative. I think that this is best reserved for metastatic tumors where the histology is already known and you want to monitor response to treatment without doing imaging.
- Moving on to circulating tumor DNA
- It has been reported that elevated concentrations of cell-free circulating tumor DNA fragments have been found in the blood plasma and serum of cancer patients. Circulating tumor DNA originate from apoptotic or necrotic tumor cells which discharge DNA into the circulation.
- In 2013, a proof of principle paper was published in the New England Journal of Medicine that demonstrated ctDNA in metastatic breast cancer patients with a detection rate of 97%. It even performed better than taking serum CA 15-3.
- A year later, a proof of principle paper for early cancers was published. In a cohort of 640 cancer patients from stage I to stage III cancers, ctDNA was picked up in 48-73%. It also said in this paper that ctDNA was detected especially in those without any circulating tumor cells, which suggested that they might be 2 separate entities.
- Proof of principle paper indicates that presence of ctDNA in pre-symptomatic individuals MIGHT become a useful screening strategy to complement more traditional, but often more invasive approaches, such as mammography and colonoscopy. For all its promises, ctDNA nevertheless presents considerable challenges. Most DNA will be coming from normal cells and ctDNA generally represents only 0.1% of the total, if not less.
- Again, since the US FDA allowed manufacturers to come up with more machines, a lot of vendors will be coming up to us and inviting us to avail of their services. But of course, not all are equal. Personally, after reading all the evidence for this, I prefer these 3 methods because they are the most sensitive.
- Advantages of ctDNA is that it just a blood test, its less labile to heat and movement than CTCs however, it still fails to identify the histology and organ of origin.
- We do offer this at Asian Hospital for this fixed amount, the name of the service is OncoTrace, basically for most cancers with an established genomic profile, turnaround time is 3-4 weeks. In its label it says that it is indicated only for stage IV patients, but then again, most studies on cancer are started out in the metastatic setting.
- At a slightly cheaper price comes OncoSelect, but it only checks for ctDNA for Nonsmall Cell Lung Cancer, Colorectal Cancer, and Breast Cancer.
- Next is CancerSEEK
- Last year, a group of doctor scientists from the Mayo Clinic presented at the European Society of Medical Oncology Annual Convention. They have developed this product called CancerSeek which screens for 8 cancers: ovary, liver, stomach, pancreas, esophagus, colorectal, lung and breast. In the Western World, these 8 cancers constitute more than 60% of their cancers. In their results, the sensitivity for these cancers were in the range of 69-98% and was specific for 99%. It is also noteworthy to say that the sensitivity for stage I liver cancer was 100%!!!
- So how does CancerSEEK work? A blood sample is drawn and the sample goes into two tests. The first test is to check for tumor mutations in the blood using ctDNA, using 16 prespecified genes. Since the problem with ctDNA is that it cannot localize where the cancer came from without any imaging, so they addressed this issue by incorporating a 31-protein panel. Then they feed all the data into their machines and algorithm. If something turns out positive, then we do some imaging, then a tissue biopsy, so we detect cancers earlier.
- Advantages of CancerSeek is that is just a blood test, it identifies the tissue of origin, it can detect early stage cancers and the scientist developed a way of making it cost effective to potentially become a routine screening tool in the future. They estimate it to be around $500 which is roughly around the cost of a colonoscopy. The disadvantages are that it only screens for only 8 cancer, false positives are noted in inflammatory and infectious conditions and there has been no large scale study on healthy control. The manufacturers are now advancing this product in a clinical trial and we will hear about the results probably in a few years time. For me, this is very promising.
- How about PET scan? People will come to me ask me if I can just do a PET CT scan for them.
- According to the American Cancer Society and the American College of Preventive Medicine: Whole body scans are a poor screening tool,Whole body scans use a lot of radiation, Whole body scans can lead to unnecessary tests and No medical societies recommend whole-body scans. The utility of PET CT scan for cancer screening can only be assessed in a prospective randomized trial. In my opinion, PET scan can complement your other tests especially if one turns out to be positive.
- I cannot end my lecture without mentioning the present guidelines for the early detection or screening of cancer because these are backed up by a lot of studies.
- Cancer screening programs have largely been implemented in high-income countries with greater available resources. However, there is a considerable variation in terms of screening methods, starting age, stopping age, and screening interval between countries.
- The guidelines which I will be presenting are the ones discussed in Harrisons, which is our Bible. And in De Vita’s Cancer Principles and Practice of Oncology, which is our textbook in Medical Oncology. These 2 textbooks discuss cancer screening guidelines made by the American Cancer Society and the US Preventive Services Taskforce (USPSTF) Both of these organizations use a formal process to review scientific evidence to create guidelines for cancer screening. The American Cancer Society guidelines peg their screening though at an earlier age, so if you want earlier detection, you follow the American Cancer Society Guidelines
- For breast cancer, they differ in the age to start testing and the frequency of mammograms. ACS recommends that women should start screening as early as 40 years old and ANNUALLY, while USPSTF recommended screening starting at 50 years old EVERY 2 YEARS
- Over the past decade we have noted an increase in the number of colorectal cancers below 50 years old, especially in patients 40 years old and above. This has led independent groups to re-examine data and just last year, the American Cancer Society brought down its age to start screening at 45 years old while USPSTF maintained its start of screening at 50 years old.
- For the direct visualization tests, again the ACS recommeded starting early at 45 years old while USPSTF recommended starting at 50 years old
- Which test do you offer to patients? The ACS and USPSTF found no head-to-head studies demonstrating that any of the screening strategies are more effective than the others and offering choice in colorectal cancer screening strategies may increase the proportion of patients who will actually do the screening.
- For cervical cancer, both ACS and USPSTF agree that screening should start at 21 years old every 3 years.
- At 30-65 years old it is an option to do a pap smear with HPV cotesting to decrease the frequency of monitoring. This is available in our hospital for around P8-9,000.
- For lung cancer screening, the American Cancer Society recommends screening between 55-74 years old while USPSTF recommends screening at 55-80 years old.
- These are the latest recommendations for prostate cancer testing. ACS and USPSTF still do not agree. ACS recommends starting at 50 years old while USPSTF recommends starting at 55 years old. Both should talk to their doctors about the pros and cons of PSA testing.
- In summary, we have entered the Golden Age of Oncology and just last year, more than 5,000 papers were published in Oncology alone. There are established ways to screen for cancer and we can always look back into our guidelines. The American Cancer Society Guidelines starts screening earlier and you might want to use this for your patients. On the other end of the spectrum, because the human genome project has been completed already, an explosion of data have been available to us because of the advent of next generation sequencing. Although these are best applied to patients with established malignancies, there are a lot of studies being done on molecular ways to look for cancer. These can be done by using multigene panels and whole genome sequencing to look for your hereditary cancer risk. Or you can actually look for circulating tumor cells or better yet, circulating tumor DNA in your blood.
- And the good news is, these are all happening in our hospital today. Thank you.