This document discusses high grade serous ovarian cancer (HGSOC), the most common and aggressive form of ovarian cancer. It provides details on:
- HGSOC is driven primarily by DNA copy number changes rather than recurrent mutations.
- Opportunities for targeted therapies exist for genomic aberrations impacting p53, homologous recombination repair, and other commonly mutated genes.
- Improving rates of complete tumor resection (R0) through a personalized surgical approach can significantly improve patient outcomes.
- Several clinical trials are exploring targeted agents and immunotherapy approaches, along with developing patient-derived xenograft models to advance precision medicine for HGSOC.
This document discusses hereditary gastrointestinal cancer syndromes. It provides background on genetics versus genomics and compares genetic testing of single genes versus multiple genes simultaneously. Lynch syndrome, also called hereditary nonpolyposis colorectal cancer, is summarized, including the importance of microsatellite instability testing and immunohistochemistry to identify mismatch repair gene mutations. Screening recommendations for Lynch syndrome, such as annual colonoscopy, are discussed to reduce cancer risk.
This document discusses tumor markers and their use in monitoring tumor response to therapy. It provides information on different types of tumor markers including proteins, enzymes, hormones, genetic markers and circulating tumor cells. Ideal tumor markers are highly sensitive and specific, correlate with tumor stage and prognosis, and can be used for screening, diagnosis, prognosis, monitoring treatment and detecting recurrence. Examples discussed include CEA, AFP, PSA, CA125 and circulating tumor cells. The Oncotype DX 21-gene recurrence score test and tissue polypeptide specific antigen are also summarized.
The document discusses recurrent ovarian cancer. It notes that the chances of recurrence vary based on initial stage, with stage III having the highest risk. Symptoms of recurrence can include abdominal bloating or pain. Recurrence is typically diagnosed through physical exam, rising CA125 levels, or imaging. Treatment depends on platinum sensitivity, and may include surgery, chemotherapy, targeted therapies, or clinical trials. One study found that initiating treatment based on rising CA125 levels alone improved progression-free and overall survival compared to waiting for symptoms.
Frédérique Penault Llorca : Oncotype DX® Breast Cancer Assay: Results and Im...breastcancerupdatecongress
This document summarizes several landmark studies that have validated the clinical utility of the Oncotype DX Breast Cancer Assay. It describes how the assay analyzes the expression of 21 genes linked to breast cancer recurrence and predicts 10-year recurrence risk and likelihood of chemotherapy benefit. Multiple large randomized controlled trials are cited that demonstrate the assay's ability to accurately prognose recurrence risk and predict response to tamoxifen versus tamoxifen plus chemotherapy based on a patient's Recurrence Score result. The assay has shown consistent results across diverse patient populations and treatment settings.
2017 ASCO RECAP: The Latest in Colorectal Cancer Research #CRCWebinarFight Colorectal Cancer
Don’t miss our recap webinar from the American Society of Clinical Oncology Annual Conference (ASCO) where we discuss the latest research and treatments for colorectal cancer patients presented during the conference.
Dr. Dustin Deming, a medical oncologist and Fight CRC Medical Advisory Board Member will guide us through his findings. Dr. Deming brings a unique perspective as a researcher, oncologist and colorectal cancer survivor. In this webinar we will dive into the research and explain what it means for those living with colorectal cancer.
Anil K. Sood, M.D., Professor
Vice Chair, Translational Research
Departments of Gynecologic Oncology and Cancer Biology
Co-Director, Center for RNAi and Non-Coding RNA
Director, Blanton-Davis Ovarian Cancer Research Program
1) Non-operative management or 'watch and wait' involves avoiding surgery for rectal cancer patients who achieve a complete clinical response after chemoradiation therapy.
2) The goal is to avoid the morbidities associated with surgery if the clinical response indicates the cancer has been eradicated.
3) Patients undergo regular examinations and imaging to monitor for tumor regrowth, with the first year involving examinations every 6-8 weeks and subsequent years every 3-6 months.
This document discusses high grade serous ovarian cancer (HGSOC), the most common and aggressive form of ovarian cancer. It provides details on:
- HGSOC is driven primarily by DNA copy number changes rather than recurrent mutations.
- Opportunities for targeted therapies exist for genomic aberrations impacting p53, homologous recombination repair, and other commonly mutated genes.
- Improving rates of complete tumor resection (R0) through a personalized surgical approach can significantly improve patient outcomes.
- Several clinical trials are exploring targeted agents and immunotherapy approaches, along with developing patient-derived xenograft models to advance precision medicine for HGSOC.
This document discusses hereditary gastrointestinal cancer syndromes. It provides background on genetics versus genomics and compares genetic testing of single genes versus multiple genes simultaneously. Lynch syndrome, also called hereditary nonpolyposis colorectal cancer, is summarized, including the importance of microsatellite instability testing and immunohistochemistry to identify mismatch repair gene mutations. Screening recommendations for Lynch syndrome, such as annual colonoscopy, are discussed to reduce cancer risk.
This document discusses tumor markers and their use in monitoring tumor response to therapy. It provides information on different types of tumor markers including proteins, enzymes, hormones, genetic markers and circulating tumor cells. Ideal tumor markers are highly sensitive and specific, correlate with tumor stage and prognosis, and can be used for screening, diagnosis, prognosis, monitoring treatment and detecting recurrence. Examples discussed include CEA, AFP, PSA, CA125 and circulating tumor cells. The Oncotype DX 21-gene recurrence score test and tissue polypeptide specific antigen are also summarized.
The document discusses recurrent ovarian cancer. It notes that the chances of recurrence vary based on initial stage, with stage III having the highest risk. Symptoms of recurrence can include abdominal bloating or pain. Recurrence is typically diagnosed through physical exam, rising CA125 levels, or imaging. Treatment depends on platinum sensitivity, and may include surgery, chemotherapy, targeted therapies, or clinical trials. One study found that initiating treatment based on rising CA125 levels alone improved progression-free and overall survival compared to waiting for symptoms.
Frédérique Penault Llorca : Oncotype DX® Breast Cancer Assay: Results and Im...breastcancerupdatecongress
This document summarizes several landmark studies that have validated the clinical utility of the Oncotype DX Breast Cancer Assay. It describes how the assay analyzes the expression of 21 genes linked to breast cancer recurrence and predicts 10-year recurrence risk and likelihood of chemotherapy benefit. Multiple large randomized controlled trials are cited that demonstrate the assay's ability to accurately prognose recurrence risk and predict response to tamoxifen versus tamoxifen plus chemotherapy based on a patient's Recurrence Score result. The assay has shown consistent results across diverse patient populations and treatment settings.
2017 ASCO RECAP: The Latest in Colorectal Cancer Research #CRCWebinarFight Colorectal Cancer
Don’t miss our recap webinar from the American Society of Clinical Oncology Annual Conference (ASCO) where we discuss the latest research and treatments for colorectal cancer patients presented during the conference.
Dr. Dustin Deming, a medical oncologist and Fight CRC Medical Advisory Board Member will guide us through his findings. Dr. Deming brings a unique perspective as a researcher, oncologist and colorectal cancer survivor. In this webinar we will dive into the research and explain what it means for those living with colorectal cancer.
Anil K. Sood, M.D., Professor
Vice Chair, Translational Research
Departments of Gynecologic Oncology and Cancer Biology
Co-Director, Center for RNAi and Non-Coding RNA
Director, Blanton-Davis Ovarian Cancer Research Program
1) Non-operative management or 'watch and wait' involves avoiding surgery for rectal cancer patients who achieve a complete clinical response after chemoradiation therapy.
2) The goal is to avoid the morbidities associated with surgery if the clinical response indicates the cancer has been eradicated.
3) Patients undergo regular examinations and imaging to monitor for tumor regrowth, with the first year involving examinations every 6-8 weeks and subsequent years every 3-6 months.
Evolution of the 21-gene Assay Oncotype DXSenology.org
This document discusses the 21-gene assay Oncotype DX, which has evolved from an experimental assay to an accepted tool for assisting treatment decisions in early-stage breast cancer. The assay measures the expression of 21 genes in breast tumor tissue via RT-PCR. Research showed the "Recurrence Score" generated by the assay is prognostic and predictive of benefit from chemotherapy, providing information beyond traditional markers. Ongoing studies are further clarifying its clinical utility. Oncotype DX is now integrated in major cancer guidelines and demonstrates clinical validity through extensive evidence from studies and use in practice.
The document provides an overview of genomics in breast cancer and summarizes the Oncotype DX genomic assay. It discusses how the assay analyzes the expression levels of 21 genes in breast tumor tissue to provide a Recurrence Score that quantifies a patient's risk of recurrence and predicts who will benefit from chemotherapy. Clinical studies have shown the assay stratifies patients into low, intermediate, and high risk groups and identifies those unlikely to benefit from chemotherapy while high risk patients see significant reduction in recurrence with chemotherapy. The assay is recommended in clinical guidelines and widely covered by insurance.
HTAi 2015 - Cost-effectiveness analysis of bevacizumab and cetuximab in advan...REBRATSoficial
This document summarizes a cost-effectiveness analysis of treatment strategies for metastatic colorectal cancer in Brazil. It finds that adding monoclonal antibodies like bevacizumab and cetuximab to chemotherapy improves survival but that the strategies are not cost-effective in Brazil's public health system as the cost per life year gained is over the hypothetical threshold of 3 times GDP per capita. The analysis uses a Markov model to compare costs and outcomes of 3 treatment sequences over a lifetime, finding that chemotherapy alone without antibodies has the best cost-effectiveness profile.
Surveillance for a Family History of Colorectal Cancerensteve
Category 1 includes those at average risk, with no family history of colorectal cancer or a single first degree relative diagnosed over age 55. Screening is a fecal occult blood test every 2 years starting at age 50.
Category 2 includes those with moderately increased risk, such as a first degree relative diagnosed under age 55 or two first or second degree relatives. Screening is colonoscopy every 5 years starting at age 50 or 10 years younger than the youngest family member's diagnosis.
Category 3 includes those at potentially high risk, with features of Familial Adenomatous Polyposis or Hereditary Non-Polyposis Colorectal Cancer. Screening is complex and individualized, often involving
This document provides an overview of the principles of immunotherapy. It begins by describing the cancer-immunity cycle and how the adaptive anticancer immune response is initiated. It then discusses how tumors can evade the immune system, such as by overexpressing inhibitory receptors like PD-L1. The document reviews different approaches to immunotherapy, including passive approaches using checkpoint inhibitors and active approaches like cancer vaccines. It also covers topics like evaluating the efficacy of immunotherapy, biomarkers, combination immunotherapy, and immune-related adverse events.
Detailed Information regarding MSKCC,IMDC score with evidence .
SSIGN Score, Fuhrman's grading described .
Prognostic significance of risk score explained
Deborah K. Armstrong, M.D., explains the newly-released patient guide for ovarian cancer patients, which was sponsored by the National Ovarian Cancer Coalition (NOCC).
Has cancer science got you stumped and overwhelmed? Leading gynecologic oncologist, Dr. Don Dizon, takes us to cancer college in this webinar. He explains the science behind ovarian cancer, how it develops, how it's diagnosed, and how ovarian cancer treatments work.
Genetic counselor, Heather Herrmann, will dive in to the topic of Lynch Syndrome & CRC. Heather has enjoyed working in both pediatric genetics and cancer genetics throughout her career. She has focused the last eight years in the area of hereditary cancer syndromes and hereditary cancer risk assessment.
Next-generation DNA sequencing (NGS) provides high-throughput sequencing of DNA fragments in parallel to determine sequences exponentially faster and cheaper than Sanger sequencing. NGS can be used for whole genome, whole exome, or targeted gene panel sequencing. It has various clinical applications including cancer screening and management, diagnosis of complex genetic diseases, and identification of pathogenic variants. Tumor mutation burden (TMB) quantifies total mutations per tumor genome and higher TMB may predict better response to immunotherapy by expressing more neoantigens.
1) HPV DNA testing offers an alternative or complement to traditional Pap smear testing for cervical cancer screening. Molecular techniques like Hybrid Capture can detect HPV infection more sensitively than Pap smears alone.
2) Studies show that HPV testing followed by Pap testing may be up to 98% sensitive for detecting cervical cancer compared to 75% for Pap testing alone. Using HPV testing as a primary screen for women over 30 could help guide patient management.
3) Target amplification techniques like PCR and signal amplification methods like Hybrid Capture are commonly used for HPV DNA testing. These methods allow for high-throughput screening and detection of multiple HPV types with varying cancer risks.
- The Personalized OncoGenomics (POG) program at the British Columbia Cancer Agency conducted whole-genome analysis on tumors from 100 patients with advanced or incurable cancers to inform treatment decisions.
- Fresh tumor and blood samples were obtained from patients and underwent whole-genome and RNA sequencing. Computational analysis identified potential driver mutations, genes and pathways.
- A multidisciplinary team discussed genomic findings weekly and established guidelines for interpreting and communicating results to integrate them into patient care. Genomic findings were considered actionable in 55 of 78 cases that underwent whole-genome analysis, and motivated treatment changes in 23 cases.
- The experience demonstrated that a multidisciplinary team can implement an approach where whole-genome
This document discusses genetic counseling for cancer risk assessment. It begins with an introduction to Sandra Brown and her role as manager of the Cancer Genetics Program. It then provides information on various genes associated with cancer risks and how damage to these genes can cause uncontrolled growth and malignant tumors. The rest of the document discusses the differences between sporadic, familial, and inherited cancers; the process of genetic counseling before and after genetic testing; recommendations for who should receive genetic counseling; challenges like interpreting results and informing family; and current issues and controversies in cancer genetics.
Colorectal cancer is the second leading cause of cancer death in western countries. Early detection through screening can prevent over 50% of deaths, but screening rates remain low. Current noninvasive screening methods like fecal occult blood tests (FOBT) have limitations in sensitivity and specificity. Blood markers like CEA, LASA, and CA19-9 are not adequate screening tools. Stool markers show more promise, like immunochemical FOBT, colonocytes, and stool DNA testing which can detect mutations. While promising, stool DNA testing needs more research on cost effectiveness and patient acceptance before being recommended for general screening. Overall, no single marker is sufficient for screening and early detection remains a challenge.
At our October webinar we spent time reviewing the importance of family history. In this webinar, we will discuss genetic and familial syndromes that are specific to colorectal cancer. We will discuss what you might look for in your family history and think about implications for prevention and management of the colorectal cancer syndromes based on this information!
About our Speakers:
Lisa Ku, MS, CGC | Certified Genetic Counselor at the University of Colorado.
Lisen Axell, MS, CGC | Certified Genetic Counselor at the University of Colorado.
1) The document discusses optimal adjuvant treatment for early stage high risk endometrial carcinoma.
2) It defines early stage high risk disease as having multiple adverse risk factors like grade 3 histology, deep myometrial invasion, lymphovascular space invasion, or lymph node metastases.
3) Treatment recommendations include pelvic radiation or vaginal brachytherapy based on risk factors, with chemotherapy also considered for very high risk cases. Ongoing trials are exploring integrating molecular markers into risk assessment and treatment decisions.
This document discusses personalized cancer therapy for ovarian cancer. It summarizes that high grade serous ovarian cancer (HGSOC) is the most common and aggressive form of ovarian cancer. HGSOC often has defects in the BRCA1/2 pathway involved in DNA repair. This makes HGSOC sensitive to PARP inhibitors, which have been FDA approved. The document also discusses developing biomarkers like the homologous recombination deficiency (HRD) score to predict which patients will respond to PARP inhibitors based on their tumor's DNA repair capabilities. Combination therapies targeting multiple pathways like the PI3K and PARP pathways are presented as a strategy to overcome resistance to targeted therapies.
CANCER of UNKNOWN PRIMARY (CUP), Dr BÙI ĐẮC CHÍhungnguyenthien
Cancer of unknown primary (CUP) refers to metastatic cancer that has spread to other parts of the body but the original primary site cannot be identified. CUP makes up approximately 2-6% of cancer cases. Conventional methods to identify the primary site include imaging scans, medical history, physical exams, and laboratory tests. Molecular profiling using techniques like immunohistochemistry, gene expression profiling, and next generation sequencing can identify predictive biomarkers and actionable targets in around 80% of CUP cases. Identifying the primary site can help determine the best treatment approach and predict outcomes. Gene expression profiling tests like the Pathwork Tissue of Origin test can determine the likely tissue of origin with 99% certainty when the highest similarity score is above
This document summarizes highlights from the Ohio Colorectal Cancer Prevention Initiative. The initiative screened over 3,300 colorectal cancer patients and found that 15.9% had defective DNA mismatch repair (dMMR). Further testing identified 4% as having Lynch syndrome (LS) and 2% as having double somatic mutations. Similar results were found in screening over 300 endometrial cancer patients. Cascade genetic testing of relatives identified over 180 additional individuals with LS. The initiative demonstrated the value of universal tumor screening in identifying hereditary cancer cases and facilitating prevention through genetic testing of relatives.
This patient presented with rectal bleeding and weight loss and was found to have stage III adenocarcinoma. Given his family history of colorectal cancer in a first-degree relative at a young age, he is at high risk for hereditary non-polyposis colorectal cancer (HNPCC). HNPCC accounts for 5-7% of colorectal cancers and results from a mutation in DNA mismatch repair genes. Individuals with HNPCC have an increased lifetime risk of colorectal and other cancers. The patient was counseled on genetic testing and increased screening for relatives is recommended.
Evolution of the 21-gene Assay Oncotype DXSenology.org
This document discusses the 21-gene assay Oncotype DX, which has evolved from an experimental assay to an accepted tool for assisting treatment decisions in early-stage breast cancer. The assay measures the expression of 21 genes in breast tumor tissue via RT-PCR. Research showed the "Recurrence Score" generated by the assay is prognostic and predictive of benefit from chemotherapy, providing information beyond traditional markers. Ongoing studies are further clarifying its clinical utility. Oncotype DX is now integrated in major cancer guidelines and demonstrates clinical validity through extensive evidence from studies and use in practice.
The document provides an overview of genomics in breast cancer and summarizes the Oncotype DX genomic assay. It discusses how the assay analyzes the expression levels of 21 genes in breast tumor tissue to provide a Recurrence Score that quantifies a patient's risk of recurrence and predicts who will benefit from chemotherapy. Clinical studies have shown the assay stratifies patients into low, intermediate, and high risk groups and identifies those unlikely to benefit from chemotherapy while high risk patients see significant reduction in recurrence with chemotherapy. The assay is recommended in clinical guidelines and widely covered by insurance.
HTAi 2015 - Cost-effectiveness analysis of bevacizumab and cetuximab in advan...REBRATSoficial
This document summarizes a cost-effectiveness analysis of treatment strategies for metastatic colorectal cancer in Brazil. It finds that adding monoclonal antibodies like bevacizumab and cetuximab to chemotherapy improves survival but that the strategies are not cost-effective in Brazil's public health system as the cost per life year gained is over the hypothetical threshold of 3 times GDP per capita. The analysis uses a Markov model to compare costs and outcomes of 3 treatment sequences over a lifetime, finding that chemotherapy alone without antibodies has the best cost-effectiveness profile.
Surveillance for a Family History of Colorectal Cancerensteve
Category 1 includes those at average risk, with no family history of colorectal cancer or a single first degree relative diagnosed over age 55. Screening is a fecal occult blood test every 2 years starting at age 50.
Category 2 includes those with moderately increased risk, such as a first degree relative diagnosed under age 55 or two first or second degree relatives. Screening is colonoscopy every 5 years starting at age 50 or 10 years younger than the youngest family member's diagnosis.
Category 3 includes those at potentially high risk, with features of Familial Adenomatous Polyposis or Hereditary Non-Polyposis Colorectal Cancer. Screening is complex and individualized, often involving
This document provides an overview of the principles of immunotherapy. It begins by describing the cancer-immunity cycle and how the adaptive anticancer immune response is initiated. It then discusses how tumors can evade the immune system, such as by overexpressing inhibitory receptors like PD-L1. The document reviews different approaches to immunotherapy, including passive approaches using checkpoint inhibitors and active approaches like cancer vaccines. It also covers topics like evaluating the efficacy of immunotherapy, biomarkers, combination immunotherapy, and immune-related adverse events.
Detailed Information regarding MSKCC,IMDC score with evidence .
SSIGN Score, Fuhrman's grading described .
Prognostic significance of risk score explained
Deborah K. Armstrong, M.D., explains the newly-released patient guide for ovarian cancer patients, which was sponsored by the National Ovarian Cancer Coalition (NOCC).
Has cancer science got you stumped and overwhelmed? Leading gynecologic oncologist, Dr. Don Dizon, takes us to cancer college in this webinar. He explains the science behind ovarian cancer, how it develops, how it's diagnosed, and how ovarian cancer treatments work.
Genetic counselor, Heather Herrmann, will dive in to the topic of Lynch Syndrome & CRC. Heather has enjoyed working in both pediatric genetics and cancer genetics throughout her career. She has focused the last eight years in the area of hereditary cancer syndromes and hereditary cancer risk assessment.
Next-generation DNA sequencing (NGS) provides high-throughput sequencing of DNA fragments in parallel to determine sequences exponentially faster and cheaper than Sanger sequencing. NGS can be used for whole genome, whole exome, or targeted gene panel sequencing. It has various clinical applications including cancer screening and management, diagnosis of complex genetic diseases, and identification of pathogenic variants. Tumor mutation burden (TMB) quantifies total mutations per tumor genome and higher TMB may predict better response to immunotherapy by expressing more neoantigens.
1) HPV DNA testing offers an alternative or complement to traditional Pap smear testing for cervical cancer screening. Molecular techniques like Hybrid Capture can detect HPV infection more sensitively than Pap smears alone.
2) Studies show that HPV testing followed by Pap testing may be up to 98% sensitive for detecting cervical cancer compared to 75% for Pap testing alone. Using HPV testing as a primary screen for women over 30 could help guide patient management.
3) Target amplification techniques like PCR and signal amplification methods like Hybrid Capture are commonly used for HPV DNA testing. These methods allow for high-throughput screening and detection of multiple HPV types with varying cancer risks.
- The Personalized OncoGenomics (POG) program at the British Columbia Cancer Agency conducted whole-genome analysis on tumors from 100 patients with advanced or incurable cancers to inform treatment decisions.
- Fresh tumor and blood samples were obtained from patients and underwent whole-genome and RNA sequencing. Computational analysis identified potential driver mutations, genes and pathways.
- A multidisciplinary team discussed genomic findings weekly and established guidelines for interpreting and communicating results to integrate them into patient care. Genomic findings were considered actionable in 55 of 78 cases that underwent whole-genome analysis, and motivated treatment changes in 23 cases.
- The experience demonstrated that a multidisciplinary team can implement an approach where whole-genome
This document discusses genetic counseling for cancer risk assessment. It begins with an introduction to Sandra Brown and her role as manager of the Cancer Genetics Program. It then provides information on various genes associated with cancer risks and how damage to these genes can cause uncontrolled growth and malignant tumors. The rest of the document discusses the differences between sporadic, familial, and inherited cancers; the process of genetic counseling before and after genetic testing; recommendations for who should receive genetic counseling; challenges like interpreting results and informing family; and current issues and controversies in cancer genetics.
Colorectal cancer is the second leading cause of cancer death in western countries. Early detection through screening can prevent over 50% of deaths, but screening rates remain low. Current noninvasive screening methods like fecal occult blood tests (FOBT) have limitations in sensitivity and specificity. Blood markers like CEA, LASA, and CA19-9 are not adequate screening tools. Stool markers show more promise, like immunochemical FOBT, colonocytes, and stool DNA testing which can detect mutations. While promising, stool DNA testing needs more research on cost effectiveness and patient acceptance before being recommended for general screening. Overall, no single marker is sufficient for screening and early detection remains a challenge.
At our October webinar we spent time reviewing the importance of family history. In this webinar, we will discuss genetic and familial syndromes that are specific to colorectal cancer. We will discuss what you might look for in your family history and think about implications for prevention and management of the colorectal cancer syndromes based on this information!
About our Speakers:
Lisa Ku, MS, CGC | Certified Genetic Counselor at the University of Colorado.
Lisen Axell, MS, CGC | Certified Genetic Counselor at the University of Colorado.
1) The document discusses optimal adjuvant treatment for early stage high risk endometrial carcinoma.
2) It defines early stage high risk disease as having multiple adverse risk factors like grade 3 histology, deep myometrial invasion, lymphovascular space invasion, or lymph node metastases.
3) Treatment recommendations include pelvic radiation or vaginal brachytherapy based on risk factors, with chemotherapy also considered for very high risk cases. Ongoing trials are exploring integrating molecular markers into risk assessment and treatment decisions.
This document discusses personalized cancer therapy for ovarian cancer. It summarizes that high grade serous ovarian cancer (HGSOC) is the most common and aggressive form of ovarian cancer. HGSOC often has defects in the BRCA1/2 pathway involved in DNA repair. This makes HGSOC sensitive to PARP inhibitors, which have been FDA approved. The document also discusses developing biomarkers like the homologous recombination deficiency (HRD) score to predict which patients will respond to PARP inhibitors based on their tumor's DNA repair capabilities. Combination therapies targeting multiple pathways like the PI3K and PARP pathways are presented as a strategy to overcome resistance to targeted therapies.
CANCER of UNKNOWN PRIMARY (CUP), Dr BÙI ĐẮC CHÍhungnguyenthien
Cancer of unknown primary (CUP) refers to metastatic cancer that has spread to other parts of the body but the original primary site cannot be identified. CUP makes up approximately 2-6% of cancer cases. Conventional methods to identify the primary site include imaging scans, medical history, physical exams, and laboratory tests. Molecular profiling using techniques like immunohistochemistry, gene expression profiling, and next generation sequencing can identify predictive biomarkers and actionable targets in around 80% of CUP cases. Identifying the primary site can help determine the best treatment approach and predict outcomes. Gene expression profiling tests like the Pathwork Tissue of Origin test can determine the likely tissue of origin with 99% certainty when the highest similarity score is above
This document summarizes highlights from the Ohio Colorectal Cancer Prevention Initiative. The initiative screened over 3,300 colorectal cancer patients and found that 15.9% had defective DNA mismatch repair (dMMR). Further testing identified 4% as having Lynch syndrome (LS) and 2% as having double somatic mutations. Similar results were found in screening over 300 endometrial cancer patients. Cascade genetic testing of relatives identified over 180 additional individuals with LS. The initiative demonstrated the value of universal tumor screening in identifying hereditary cancer cases and facilitating prevention through genetic testing of relatives.
This patient presented with rectal bleeding and weight loss and was found to have stage III adenocarcinoma. Given his family history of colorectal cancer in a first-degree relative at a young age, he is at high risk for hereditary non-polyposis colorectal cancer (HNPCC). HNPCC accounts for 5-7% of colorectal cancers and results from a mutation in DNA mismatch repair genes. Individuals with HNPCC have an increased lifetime risk of colorectal and other cancers. The patient was counseled on genetic testing and increased screening for relatives is recommended.
nside Myriad. At Myriad, our goal is to make a difference in patients' lives and our work has been guided by this mission throughout the Company's history. ... Since 1991, Myriad has invested heavily in educating patients and healthcare professionals about the role genes and proteins play in disease.
Genetics and "Genomics" Dr. Roisin O’Cearbhaill slidesbkling
The words genetics and “genomics” are sometimes used interchangeably, but what exactly do these two terms mean and how are they different?
This program will help unpack the confusion surrounding these very different forms of testing. Join Peggy Cottrell, MS, CGC, board certified genetic counselor at Sharsheret and Dr. Roisin O’Cearbhaill, Research Director of the Gynecologic Medical Oncology Service at Memorial Sloan Kettering Cancer Center (MSKCC), as they explain the types of tests you may have had and what tests you should consider.
Douglas Riegert-Johnson discusses screening and referral for genetic diseases. Primary care providers should obtain a detailed cancer family history including cancer types and ages of diagnosis. Patients meeting certain criteria like breast cancer under age 50 or multiple primaries should be referred for genetic counseling. All colon cancer patients should now undergo tumor testing for Lynch syndrome. Genetic counselors can be located through the National Society of Genetic Counselors website. While genetic testing is advancing, randomized controlled trials are needed to establish clinical utility.
This document summarizes the management of pancreatic carcinoma. It discusses the anatomy, epidemiology, risk factors, hereditary syndromes, pathophysiology including pre-cancerous lesions, types of pancreatic cancer, staging, prognostic factors, diagnostic techniques, treatment including surgery, chemotherapy, targeted therapy, radiotherapy and historical prospective studies. It provides a comprehensive overview of pancreatic carcinoma covering all relevant aspects of the disease.
This document discusses the changing landscape of cancer of unknown primary (CUP) over four decades from 1976 to the present. It describes the evolution from recognition of favorable prognostic subsets in 1976-1986, to improved diagnostic techniques in 1986-1996, to empiric chemotherapy in 1996-2006, and currently to improved pathologic and genetic diagnostic technologies and better outcomes for many CUP patients from 2006 onward. The document provides details on histologic classification, clinicopathologic entities, diagnostic approaches including imaging, histopathology, immunohistochemistry, and molecular analysis, as well as discussion of favorable and unfavorable prognostic subsets and treatment approaches.
Based on the clinical findings and investigations, the differential diagnoses in this case include:
1. Advanced ovarian malignancy
2. Tubo-ovarian abscess
3. Advanced uterine malignancy
4. Advanced gastrointestinal malignancy
The investigations that should be advised include:
1. Tumor markers (CA 125, CEA, CA 19-9)
2. Abdominal and pelvic ultrasound/ CT scan to look for primary site and metastases
3. Chest X ray
4. Colonoscopy
Considering the age of the patient, elevated tumor markers, splenomegaly on USG and restricted mobility of mass on examination, advanced ovarian malignancy seems to be the likely diagnosis
BRCA – Importance in Hereditary Breast & Ovarian CancerLifecare Centre
BRCA – Importance in Hereditary
Breast & Ovarian Cancer
DGF & WOW India
presentation was made by
Dr Sharda Jain
based on presentation made by
Dr Sunil Tadepalli
Current knowledge and state of the art about management of abnormal cervical Cancer screening tests and cancer precursors for health providers in low-income settings is presented.
РREMALIGNANT AND MALIGNANT DISORDERS OF THE CERVIX.pdfSyazwaniPiti
This document discusses premalignant and malignant disorders of the cervix. It begins by explaining that cervical cancer is caused by HPV, which is transmitted sexually and can remain dormant for many years before causing cervical neoplasia. It then lists cervical cancer risk factors and discusses HPV types. The remainder of the document covers topics like HPV testing, Pap smear procedures, the Bethesda classification system for cervical cytology, management of abnormal Pap results, the pathogenesis and treatment of cervical intraepithelial neoplasia (CIN), and natural history and treatment options for CIN.
This document discusses genetics implications for survivorship programs. It highlights identifying patients who were previously missed for genetic testing and may benefit from re-testing given advances in panel testing. It also reviews managing hereditary cancer risks and addressing the psychosocial issues patients face, such as making difficult medical decisions, informing relatives, and dealing with feelings of guilt. Survivorship programs can help such patients navigate these medical and familial implications.
This document discusses the role of surgery in preventing hereditary cancers. It describes several hereditary cancer syndromes where prophylactic surgery can significantly reduce cancer risk, including breast cancer associated with BRCA1/2 mutations and diffuse gastric cancer associated with CDH1 mutations. For these high-risk conditions, the document reviews cancer risks, genetic testing approaches, screening options, and evidence regarding risk-reducing surgeries such as mastectomy and gastrectomy. It provides guidance on identifying appropriate candidates and timing for preventive surgical interventions.
Chapter 38 role of surgery in cancer preventionNilesh Kucha
The document discusses the role of surgery in preventing cancers caused by hereditary genetic mutations. It focuses on several high-risk cancer syndromes including BRCA1/2 mutations which increase breast and ovarian cancer risk, CDH1 mutations which increase stomach cancer risk, and APC mutations which cause Familial Adenomatous Polyposis (FAP) and increase colon cancer risk. For each, it describes the associated cancer risks, genetic testing recommendations, surveillance guidelines, and risk-reducing surgical options such as prophylactic mastectomies, salpingo-oophorectomies, and gastrectomies. The timing of such surgeries is based on the earliest age of cancer onset in the
Chapter 5 hereditary cancer syndrome next generationNilesh Kucha
This document provides an overview of hereditary cancers and genetic testing. It discusses:
- The difference between sporadic and hereditary cancers, with hereditary cancers making up 10% of cases and being caused by germline mutations passed down from a parent.
- Several hereditary cancer syndromes are described in detail, including BRCA1/2 associated with breast and ovarian cancer, Li-Fraumeni syndrome, Cowden syndrome, and Lynch syndrome.
- Surveillance recommendations are provided for each syndrome to enable early cancer detection.
- The role of genetic testing is discussed to identify mutations that cause hereditary cancer syndromes and guide patient management.
This document summarizes a presentation on genetic testing for cancer risk. The presentation covered:
- The role of genetic cancer risk assessment in identifying inherited cancer risk.
- Common hereditary cancer syndromes like BRCA1/2 and Lynch syndrome and their associated cancer risks.
- Guidelines for cancer screening and management based on genetic test results.
- The benefits and limitations of multi-gene cancer panels.
- How to interpret genetic test results and provide appropriate risk management recommendations to patients.
The document outlines the rationale and protocol for a study investigating micrometastases in pN0 colon cancer patients. It notes high recurrence rates in this group and aims to 1) improve risk stratification and 2) study the impact of adjuvant chemotherapy for pN0micro+ patients. The proposed study is a multicenter, randomized clinical trial that will examine lymph nodes from pN0 colon cancer patients using serial sectioning and immunohistochemistry to detect micrometastases, and randomize pN0micro+ patients to observation or adjuvant chemotherapy to evaluate 3-year disease-free survival.
Similar to 2020 Update In Hereditary Cancer Syndromes (20)
This patient has recurrent abdominal pain or discomfort at least one day per week in the last three months associated with two or more of the following criteria: 1) related to defecation, 2) associated with a change in frequency of stool, 3) associated with a change in form (appearance) of stool. This meets the Rome IV criteria for irritable bowel syndrome.
Sessile serrated polyps, or SSPs, are associated with interval colon cancers. SSPs represent about 10% of colon polyps and have a "boot-shaped" histopathology. They are often incompletely resected, with around 50% of large SSPs (10-20mm) being incompletely removed. Recognizing and completely removing SSPs is important due to their relevance as markers for missed lesions and future neoplasia. Proper technique including retroflexion examination of the right colon can help increase detection rates. Follow-up recommendations after removal are similar to adenomas, with larger SSPs requiring surveillance in 3 years. Serrated polyposis syndrome,
This document discusses the evaluation and management of Peutz-Jeghers Syndrome (PJS) through several case studies. It describes the key features of PJS including melanotic macules, stalked polyps most commonly in the small bowel, and polyps containing arborizing smooth muscle. It emphasizes that genetic testing has limited sensitivity for PJS and family history may be uninformative in half of cases. The document stresses individualized cancer screening based on risk and the importance of double balloon endoscopy to identify and remove precancerous polyps from the small bowel in PJS patients.
Precision medicine involves using genomic testing to individualize medical care by testing multiple genes at once. Genomic counseling is the process of obtaining a family history, formulating a testing strategy, providing counseling on potential outcomes, coordinating testing, and disclosing results. Key steps include referring to a genomic counselor, who will discuss testing options and implications of various results, order the appropriate tests, track the results, and arrange follow-up care. Genomic information can guide medical management and reproductive decision making for patients and their families.
This document summarizes key information about sessile serrated adenomas (SSAs):
1. SSAs represent approximately 1 in 10 colon polyps and are important because of their association with interval colon cancers, which may be due to not seeing these lesions, finding new lesions, or incompletely resecting earlier lesions.
2. Surveillance guidelines for SSAs are similar to those for adenomas, with follow up intervals ranging from 1-5 years depending on size and number of polyps.
3. Serrated polyposis syndrome, defined by having multiple large serrated polyps, requires yearly colonoscopy surveillance due to the high risk of future neoplasia.
1) Colonoscopy reduces colon cancer rates in Lynch syndrome patients by detecting and removing precancerous polyps, but the effectiveness depends on the colonoscopist's adenoma detection rate.
2) The accepted quality marker is an adenoma detection rate above 25% for men and 15% for women. Patients should seek colonoscopists meeting these benchmarks.
3) For Lynch syndrome patients, colonoscopies should include intensive inspection of the right side of the colon and consider chromoendoscopy to aid in visualizing small polyps.
Companion slideshow for polyppolyp.com (Familial adenomatous polyposis)Douglas Riegert-Johnson
A companion slideshow to the polypolyp.com website. The website is designed to assist in polyposis care, education and documentation. (c) 2014 Douglas Riegert-Johnson.
Hereditary breast and ovarian cancer clinic visit visual aids (Mayo Clinic Fl...Douglas Riegert-Johnson
The document summarizes information about hereditary breast and ovarian cancer syndrome (HBOC). It finds that 10-25% of breast cancer and 5-10% of ovarian cancer is considered hereditary. The majority of HBOC cases, around 84%, are caused by mutations in the BRCA1 and BRCA2 genes. Carriers of BRCA1 and BRCA2 mutations have significantly increased lifetime risks of developing breast cancer (56-87% for both genes) and ovarian cancer (44% for BRCA1, 27% for BRCA2) compared to the general population. Genetic testing for BRCA1 and BRCA2 mutations is available to assess cancer risk and guide risk-reducing medical or
The document summarizes information about hereditary breast and ovarian cancer syndrome (HBOC). It finds that 10-25% of breast cancer and 5-10% of ovarian cancer is considered hereditary. The majority of HBOC cases, around 84%, are caused by mutations in the BRCA1 and BRCA2 genes. Carriers of BRCA1 and BRCA2 mutations have significantly increased lifetime risks of developing breast cancer (56-87% for both genes) and ovarian cancer (44% for BRCA1, 27% for BRCA2) compared to the general population. Genetic testing for BRCA1 and BRCA2 mutations is available to assess cancer risk and guide risk-reducing medical or
This document discusses two case studies of patients presenting with polyposis and other features. The first case is a 45-year-old man who previously had colon polyps and jejunal adenocarcinoma. Genetic testing was negative for familial adenomatous polyposis (FAP). The second case details a family with a history of colon cancer and a brain tumor. Genetic testing found the patient has a constitutional mismatch repair deficiency (CMMRD), also known as Turcot syndrome, caused by biallelic mutations in the PMS2 gene. CMMRD is characterized by colon polyps and brain tumors occurring at a young age. The document provides background on Turcot syndrome and compares the features
1) The document discusses genetic colon cancer syndromes familial adenomatous polyposis (FAP) and Lynch syndrome (LS), providing definitions, terminology, guidelines, and case examples.
2) For FAP, it recommends monitoring for iron/B12 deficiencies annually in patients and considers chemoprevention with fish oil. For retained rectum in FAP, surveillance is every 6 months.
3) For LS, it states the emerging standard is universal microsatellite instability testing on all or most colon cancers to identify cases, rather than relying on clinical criteria alone.
Adhd Medication Shortage Uk - trinexpharmacy.comreignlana06
The UK is currently facing a Adhd Medication Shortage Uk, which has left many patients and their families grappling with uncertainty and frustration. ADHD, or Attention Deficit Hyperactivity Disorder, is a chronic condition that requires consistent medication to manage effectively. This shortage has highlighted the critical role these medications play in the daily lives of those affected by ADHD. Contact : +1 (747) 209 – 3649 E-mail : sales@trinexpharmacy.com
Local Advanced Lung Cancer: Artificial Intelligence, Synergetics, Complex Sys...Oleg Kshivets
Overall life span (LS) was 1671.7±1721.6 days and cumulative 5YS reached 62.4%, 10 years – 50.4%, 20 years – 44.6%. 94 LCP lived more than 5 years without cancer (LS=2958.6±1723.6 days), 22 – more than 10 years (LS=5571±1841.8 days). 67 LCP died because of LC (LS=471.9±344 days). AT significantly improved 5YS (68% vs. 53.7%) (P=0.028 by log-rank test). Cox modeling displayed that 5YS of LCP significantly depended on: N0-N12, T3-4, blood cell circuit, cell ratio factors (ratio between cancer cells-CC and blood cells subpopulations), LC cell dynamics, recalcification time, heparin tolerance, prothrombin index, protein, AT, procedure type (P=0.000-0.031). Neural networks, genetic algorithm selection and bootstrap simulation revealed relationships between 5YS and N0-12 (rank=1), thrombocytes/CC (rank=2), segmented neutrophils/CC (3), eosinophils/CC (4), erythrocytes/CC (5), healthy cells/CC (6), lymphocytes/CC (7), stick neutrophils/CC (8), leucocytes/CC (9), monocytes/CC (10). Correct prediction of 5YS was 100% by neural networks computing (error=0.000; area under ROC curve=1.0).
Histololgy of Female Reproductive System.pptxAyeshaZaid1
Dive into an in-depth exploration of the histological structure of female reproductive system with this comprehensive lecture. Presented by Dr. Ayesha Irfan, Assistant Professor of Anatomy, this presentation covers the Gross anatomy and functional histology of the female reproductive organs. Ideal for students, educators, and anyone interested in medical science, this lecture provides clear explanations, detailed diagrams, and valuable insights into female reproductive system. Enhance your knowledge and understanding of this essential aspect of human biology.
These lecture slides, by Dr Sidra Arshad, offer a quick overview of the physiological basis of a normal electrocardiogram.
Learning objectives:
1. Define an electrocardiogram (ECG) and electrocardiography
2. Describe how dipoles generated by the heart produce the waveforms of the ECG
3. Describe the components of a normal electrocardiogram of a typical bipolar lead (limb II)
4. Differentiate between intervals and segments
5. Enlist some common indications for obtaining an ECG
6. Describe the flow of current around the heart during the cardiac cycle
7. Discuss the placement and polarity of the leads of electrocardiograph
8. Describe the normal electrocardiograms recorded from the limb leads and explain the physiological basis of the different records that are obtained
9. Define mean electrical vector (axis) of the heart and give the normal range
10. Define the mean QRS vector
11. Describe the axes of leads (hexagonal reference system)
12. Comprehend the vectorial analysis of the normal ECG
13. Determine the mean electrical axis of the ventricular QRS and appreciate the mean axis deviation
14. Explain the concepts of current of injury, J point, and their significance
Study Resources:
1. Chapter 11, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 9, Human Physiology - From Cells to Systems, Lauralee Sherwood, 9th edition
3. Chapter 29, Ganong’s Review of Medical Physiology, 26th edition
4. Electrocardiogram, StatPearls - https://www.ncbi.nlm.nih.gov/books/NBK549803/
5. ECG in Medical Practice by ABM Abdullah, 4th edition
6. Chapter 3, Cardiology Explained, https://www.ncbi.nlm.nih.gov/books/NBK2214/
7. ECG Basics, http://www.nataliescasebook.com/tag/e-c-g-basics
TEST BANK For Community Health Nursing A Canadian Perspective, 5th Edition by...Donc Test
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TEST BANK For Basic and Clinical Pharmacology, 14th Edition by Bertram G. Kat...rightmanforbloodline
TEST BANK For Basic and Clinical Pharmacology, 14th Edition by Bertram G. Katzung, Verified Chapters 1 - 66, Complete Newest Version.
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TEST BANK For Basic and Clinical Pharmacology, 14th Edition by Bertram G. Katzung, Verified Chapters 1 - 66, Complete Newest Version.
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3. 2020 is the year of the HCS! “MORE.”
More testing.
More different tests.
More diagnoses.
More natural history data.
More treatments.
4. 2020 is the year of the HCS!
• HCS Background - HCS at Mayo Clinic Florida
• Diagnosis
• Panel testing
• Accessibility
• Accuracy (DNA + mRNA sequencing)
• Clarifying the natural history
• PALB2
• Lynch syndrome
• Pheochromocytoma and paraganglioma syndromes
• Management
5. Hereditary Cancer Syndromes (HCS)
• MCs INTERCEPT trial recently tested about 3,000 newly
diagnosed cancer patients for a HCS. PI Dr. Samadder (MCA)
will present those results at a CIM grand rounds later this year.
• HCS are a diverse group of about 100 disorders predisposing
to both benign and malignant tumors. HCS are each
associated with germline pathogenic variants in a single gene
(eg BRCA1). They are usually associated with an increased
risk of cancer from at least two different organ systems. Eg
Lynch syndrome – colon and uterine.
• The population prevalence is about 2%, in individuals with
cancer the overall prevalence is about 10%.
6. High risk HCS (OR >4-5)
are less common than intermediate risk HCS.
High risk syndromes (BRCA1/2) about 1/300.
Intermediate risk syndrome (CHEK2) 1%
PDQ cancer summaries
https://www.ncbi.nlm.nih.gov/books/NBK65761/
7. Hereditary Cancer Syndromes
at Mayo Clinic Florida.
HCS are seen in many clinics, and not all patients are seen in
Cancer Genetics. Cancer Genetics has seen about 800 patients
with about 60 different diagnoses in 12 years.
Mayo Clinic Florida
Cancer Syndrome Patient Panel 779
Lynch syndrome 161
Familial Adenomatous Polyposis 156
BRCA1/2 mutation carriers 127
Peutz Jeghers syndrome 36
CHEK2 38
8. Some HCS are very rare.
Sample of HCS were
Only 1 or 2 patients have been seen (2008-2020)
Gastric adenocarcinoma and proximal
polyposis of the stomach
BAP1
Dyskeratosis congenita HOXB12
RAD51D CEBPA
MITF AXIN2
MODY type 3 NTHL1 Biallelic mutations
Familial esophageal cancer RAD50
Schwanomatosis NBN
Familial CLL CHEK2 pathogenic variant homozygous
Rothmund-Thompson Syndrome Familial esophageal cancer
11. Who to test? Offer testing to all.
In general, clinical decision tools do not have the power to a pathogenic
HCS variant. Said another way, they can not identify a group of patients
with less than a 1% chance of having a positive test.
12. What test to order?
A Large number of Genes.
0
2
4
6
8
10
12
14
16
18
20
Small No. Genes Medium No.
Genes
Large No. Genes
Percentage of Patients with Pathogenic Variant
Large Panel
• Diagnoses more patients
• No difference in OP, TAT
• Lab is probably doing large panel. Easier to have the same workflow on all
patients
13. Case 2020:
Value of Large
HCS Panel.
2 PVS!
• 37 yo female with Stage
IIB breast adenoCA
• BRCA2 PV and
hereditary Pheo/Para
SDHD PV
• PET/CT – Right cartiod
body bifurcation uptake
14. Accessibility
• Accessibility.
• Cost
• Most cancer patients have no out of pocket.
• Out of pocket maximum is $250 for most tests.
• Availability to an ordering provider.
• Color.com and others offer HCS panel testing via mail (saliva kit)
ordered by their providers ($250).
• As testing is ordered by provider after patient initiation, FDA approval is
not needed. Direct to consumer testing (23andme) does need FDA
approval.
• >200,000 ? HCS tests / year
Cynthia Nelson
Multi-Gene Panel Testing of 23,179 Individuals . .
Journal of Molecular Diagnostics 2019
15. RNA testing allows interpretation of splice site variants
and discovery of deep intronic pathogenic variants.
PMS2 c.11C>G
VUS->VLP
ATM c.2466A>G
VUS->VLB
ATM c.3065T>G
VUS->VLP
BRCA2 c.475+4DELT
VUS->VLP
BRCA1 c.81-9C>G
VUS->Pathogenic
BRCA1 c.5152+6T>G
VUS->Pathogenic
APC c.933+829A>G
Pathogenic
ATM
c.2466+1552G
>C
VLP
ATM c.497-2661A>G
VLP
Splicing profile by capture RNA-seq identifies
pathogenic germline variants in tumor
suppressor genes; NPJ Precis Oncol. 2020
16. DNA testing + RNA sequencing
• 1000 clinical samples for testing of 18 tumor suppressor
genes
• DNA testing> 77 pathogenic or likely pathogenic
• DNA + RNA testing> 84 pathogenic or likely pathogenic
(+9.4%).
• Results are used to improve interpretation of follow up
results and also the DNA testing (deep intronic mutations
are added to regular DNA panel)
• RNA testing has not been validated on saliva.
Landrith
Precision Oncology 2020
19. The Prospective Lynch Syndrome
Database
• About 50,000 years of patient follow up.
• Clinical scenario:
30 yo MSH2 carrier has read that Lynch syndrome is
associated with urinary tract cancers and asks about
having a urinalysis?
Pål Møller
The Prospective Lynch Syndrome Database reports enable evidence-based personal precision health care
Hereditary Care Clin Pract 2020
22. May 2020 “… correlations between
PALB2 mutations and increased
risks of ovarian cancer, pancreatic
cancer, prostate, and male breast
cancer have been suggested;
however these exact risks are
subject to further study.”
23.
24. SS risk for female breast cancer, male breast
cancer, ovarian cancer and pancreas ID.
25. Germline mutations are not uncommon in
individuals with Pheo/Para
• About 30% of patients will have a germline mutation in
one of ten genes.(Under 10 yo – 90%, Over 60 – 20%)
• In adults, SDH family genes are the most commonly
mutated.
Hartmut Newman and others.
Pheochromocytoma and Paraganglioma.
NEJM 2019
26. Clinical Scenario.
• 39 yo man
• Age 33 resection of HNP
• HCS panel testing found the SDHD P81L founder mutation
• Clinical question,
• What is the risk of a pheochromocytoma or intra adbominal
paraganglioma? How often does he need follow up imaging of the
abdomen?
27. P81L SDHD pathogenic variant carriers are at low risk for
pheochromocytomas and abdominal paragangliomas.
Bayley and others.
Variant type is associated with disease characteristics in SDHB …
J Med Genetics 2020
29. Endoscopic Management of
Familial Adenomatous Polyposis
• FAP is associated intestinal polyps, especially
colon polyps, thyroid cancer, desmoid tumors,
osteomas and other tumors.
• Attenuated FAP (aFAP)
• Less than 100 adenomatous polyps.
• Usual treatment for aFAP is a subtotal colectomy (rectum left in
place).
• Classic FAP
• More than 100 adenomatous polyps
• Usual treatment is a total colectomy usually with a J pouch (“new”
rectum created out of ileum.)
30. Endoscopic Management of
Familial Adenomatous Polyposis
• 95 FAP patients who refused surgery managed
endoscopically for mean of 5.1 years.
• Removed 55,701 polyps.
• No invasive cancers.
• 2 patients sent to surgery for carpeting polyposis not
amenable to endoscopic management.
Hideki Ishikawa
Endoscopic Management of Familial Adenomatous Polyposis in Patients Refusing Colectomy
Endoscopy 2016
31.
32. Endoscopic management of AFAP
23 yo (2011) year old patient presented
with retro orbital osteoma.
Year Number of colon polyps removed
2011 30
2012 14
2013 26
2014 15
2015 15
2016 24
2017 31
2018 7 (poor preparation)
2019 35
33. Clinical Scenario
• 43 woman with both BRCA1 and CHEK2 pathogenic
variants. Her mother died of ovarian cancer at 59 years of
age and a maternal aunt died of ovarian cancer at age 50
years of age.
• She has declined RR (risk reducing) BSO due to
concerns of the adverse effects.
• What to do?
34. For BRCA1/2 patients, BS/DO vs RRSO
• BS/DO= Bilateral salpingectomy with delayed
oophorectomy
• RRSO= Risk reducing salpingectomy/oophorectomy
• Current 3.2019 NCCN recommendations are,
• BRCA1 RRSO age 35-40
• BRCA2 RRSO age 40-45
35. Ovarian malignancies in BRCA1/2 carriers usually
originate from ends of the fallopian tubes.
• 2001, 6 of 12 women with BRCA and other ovarian cancer
predispositions undergoing RRS were found to have
dysplasia at the tips of the fallopian tubes (fimbria).
Piek JM.
Dysplastic changes in prophylactically removed fallopian tubes.
J Pathol (2001)
Patricia Shaw
Candidate Serous Cancer Precursors in Fallopian Tube Epithelium of BRCA1/2 Mutation Carriers
Mod Path 2009
Iiana Cass
A Cautious View of Putative Precursors of Serous Carcinomas in the Fallopian Tubes of BRCA Mutation Carriers
Gyne Oncol 2014
Michael Callahan
Primary Fallopian Tube Malignancies in BRCA-Positive Women Undergoing Surgery for Ovarian Cancer
Journal of Clinical Oncology 2007
Center Year Number of
BRCA1/2 BSO
% with fallopian tube
neoplasia
Toronto 2009 176 8
Brigham & Women’s 2007 122 5.7
Cedars Sinai 2014 78 12
36.
37. Final Results Pending From Prospective Trials
of Risk Reducing Salpingectomy
and Delayed Oophorectomy
Participants choose either standard RRSO within current guidelines (at
age 35-40 years for BRCA1 carriers, age 40-45 years for BRCA2
carriers)
or the innovative RR salinpectomy approach followed by RRO
at up to 5 years after the current guideline age (at age 40-45 years for
BRCA1 carriers, age 45-50 years for BRCA2 carriers).
• WISP - MD Anderson
• 183 patients with BRCA1/2 or other ovarian cancer predisposition genes
• TUBA trial- Launched at 13 Dutch oncology centers in 2015
• Plans to enroll 510 BRCA1/2 mutation carriers.
• NCCN 3.2019 “BS/DO is not the standard of care, as some risk is still
present and in women who have not had RR breast surgery
oophorectomy decreases cancer risk.”
38. Clinical Scenario
• 43 woman with both BRCA1 and CHEK2 pathogenic
variants. Her mother died of ovarian cancer at 59 years of
age and a maternal aunt died of ovarian cancer at age 50
years of age.
• She has declined RR (risk reducing) BSO due to
concerns of the adverse effects.
• What to do?
Patient opted for risk reducing bilateral salpingectomy, with
delayed oophorectomy.
42. 2020 is the year of the HCS! MORE.
• More testing
• Cheaper
• More different tests.
• Large panels.
• RNA testing.
• More diagnoses.
• More natural history data.
• Completion of large studies.
• More treatments.
The ATM gene was recently identified and found to be responsible for the human genetic disorder ataxia-telangiectasia. The major ATM transcript is 13 kb. Using long-distance PCR, we determined the genomic structure of this gene and identified all of its exon–intron boundaries. The ATM gene spans approximately 150 kb of genomic DNA and consists of 66 exons. The initiation codon falls within exon 4. The last exon is 3.8 kb and contains the stop codon and a 3′-untranslated region of about 3600 nucleotides.
The eligible families included 8,830 females (852 with
PALB2 PVs) and 9,076 males.