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touchMDT Implementing a personalized approach to treatment of thyroid cancer: the importance of biomarker testing and targeted therapies

Watch leading specialists within an MDT discuss the importance of biomarker testing and targeted therapies for personalizing management of thyroid cancer

 Overview & Learning Objectives

Patient with thyroid cancer
Oncologist, endocrinologist, pathologist, and nurse
Watch Video
Thyroid cancers and role of the MDT Dr L Wirth, Dr A Matrone, Dr P Sadow, Ms T Hurley

Watch an oncologist, an endocrinologist, a pathologist and an oncology nurse specialist discuss the main types of thyroid cancer and its epidemiology, the unmet treatment need, new and emerging targeted therapies, and the role of the multidisciplinary team in patient care.

Watch Video
Pathologist, endocrinologist, and oncologist
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Biomarker testing in personalized care Dr P Sadow, Dr A Matrone, Dr L Wirth

A pathologist, an endocrinologist and an oncologist discuss the use of biomarkers in thyroid cancer care and how personalized medicine influences patient outcomes. This video contains a patient case study.

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Endocrinologist, oncologist, and nurse
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Clinical data for targeted therapies Dr A Matrone, Dr L Wirth, Ms T Hurley

Watch an endocrinologist, an oncologist and an oncology nurse specialist discuss the latest efficacy and safety data from recent clinical trials for targeted therapies for thyroid cancer. This video contains patient case studies.

Watch Video
Oncologist, endocrinologist, pathologist, and nurse

Watch an oncologist, an endocrinologist, a pathologist and an oncology nurse specialist discuss the main types of thyroid cancer and its epidemiology, the unmet treatment need, new and emerging targeted therapies, and the role of the multidisciplinary team in patient care.
Expert Spotlight
Dr Lori Wirth
Massachusetts General Hospital, Boston, MA, USA
Dr Antonio Matrone
University of Pisa, Pisa, Italy
Dr Peter Sadow
Massachusetts General Hospital, Boston, MA, USA
Ms Tara Hurley
The Royal Marsden NHS Foundation Trust, Sutton, UK

An oncologist, an endocrinologist, a pathologist and an oncology nurse specialist discuss the epidemiology of thyroid cancer, available treatment options, and the role of the multidisciplinary team in patient care.

Listen on the go

 Learn more Back to MDT Hub Time: 15:17
 
Pathologist, endocrinologist, and oncologist

A pathologist, an endocrinologist and an oncologist discuss the use of biomarkers in thyroid cancer care and how personalized medicine influences patient outcomes. This video contains a patient case study.
Expert Spotlight
Dr Peter Sadow
Massachusetts General Hospital, Boston, MA, USA
Dr Antonio Matrone
University of Pisa, Pisa, Italy
Dr Lori Wirth
Massachusetts General Hospital, Boston, MA, USA

A pathologist, an endocrinologist and an oncologist discuss the use of biomarkers in thyroid cancer care and how personalized medicine influences patient outcomes. This video contains a patient case study.

Listen on the go

 Learn more Back to MDT Hub Time: 16:17
 
Endocrinologist, oncologist, and nurse

Watch an endocrinologist, an oncologist and an oncology nurse specialist discuss the latest efficacy and safety data from recent clinical trials for targeted therapies for thyroid cancer. This video contains patient case studies.
Expert Spotlight
Dr Antonio Matrone
University of Pisa, Pisa, Italy
Dr Lori Wirth
Massachusetts General Hospital, Boston, MA, USA
Ms Tara Hurley
The Royal Marsden NHS Foundation Trust, Sutton, UK

An endocrinologist, an oncologist and an oncology nurse specialist discuss the latest efficacy and safety data for targeted therapies for thyroid cancer. This video contains patient case studies.

Listen on the go

 Learn more Back to MDT Hub Time: 17:26
 
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Overview & Learning Objectives
Overview

In this activity, specialists from MDTs involved in caring for patients with thyroid cancer share their perspectives on biomarker testing and its influence on patient outcomes, and what the latest data for targeted therapies tell us about the prospects for patients with the disease.

This activity is jointly provided by USF Health and touchIME. read more

Target Audience

This activity has been designed to meet the educational needs of oncologists, pathologists, radiologists and oncology specialist nurses involved in the care of patients with thyroid cancer.

Disclosures

USF Health adheres to the Standards for Integrity and Independence in Accredited Continuing Education.

All individuals in a position to influence content have disclosed to USF Health any financial relationship with an ineligible organization. USF Health has reviewed and mitigated all relevant financial relationships related to the content of the activity. Relevant relationships are listed below. All individuals not listed have no relevant financial relationships.

Faculty

Dr Antonio Matrone discloses Advisory board and panel fees from Eli Lilly.

Dr Lori Wirth discloses Advisory board and panel fees from Bayer HealthCare Pharmaceuticals, Blueprint Medicines, Eli Lilly and Exelixis. Consultancy fees from Eisai.

Dr Peter Sadow discloses Consultancy fees from Bayer and Veracyte.

Ms Tara Hurley has no interests/relationships or affiliations to disclose in relation to this activity.

Content reviewer

Alicia Canalejo, APRN has no financial interests/relationships or affiliations in relation to this activity.

Touch Medical Director

Sola Neunie has no financial interests/relationships or affiliations in relation to this activity.

USF Health Office of Continuing Professional Development and touchIME staff have no financial interests/relationships or affiliations in relation to this activity.

Requirements for Successful Completion

In order to receive credit for this activity, participants must review the content and complete the post-test and evaluation form. Statements of credit are awarded upon successful completion of the post-test and evaluation form.

If you have questions regarding credit please contact cpdsupport@usf.edu 

Accreditations

Physicians

This activity has been planned and implemented in accordance with the accreditation requirements and policies of the Accreditation Council for Continuing Medical Education (ACCME) through a joint providership of USF Health and touchIME. USF Health is accredited by the ACCME to provide continuing medical education for physicians.

USF Health designates this enduring material for a maximum of 1.0 AMA PRA Category 1 CreditTM.  Physicians should claim only the credit commensurate with the extent of their participation in the activity.

The European Union of Medical Specialists (UEMS) – European Accreditation Council for Continuing Medical Education (EACCME) has an agreement of mutual recognition of continuing medical education (CME) credit with the American Medical Association (AMA). European physicians interested in converting AMA PRA Category 1 CreditTM into European CME credit (ECMEC) should contact the UEMS (www.uems.eu)

Advanced Practice Providers

Physician Assistants may claim a maximum of 1.0 Category 1 credits for completing this activity. NCCPA accepts AMA PRA Category 1 CreditTM from organizations accredited by ACCME or a recognized state medical society.

The AANPCP accepts certificates of participation for educational activities approved for AMA PRA Category 1 CreditTM by ACCME-accredited providers. APRNs who participate will receive a certificate of completion commensurate with the extent of their participation.

Nurses

USF Health is accredited as a provider of nursing continuing professional development by the American Nurses Credentialing Center’s Commission on Accreditation.

A maximum of 1.0 contact hour may be earned by learners who successfully complete this continuing professional development activity. USF Health, the accredited provider, acknowledges touchIME as the joint provider in the planning and execution of this CNE activity.

This activity is awarded 1.0 ANCC pharmacotherapeutic contact hour.

Date of original release: 29 November 2021. Date credits expire: 29 November 2022.

If you have any questions regarding credit please contact cpdsupport@usf.edu

Learning Objectives

After watching this activity, participants should be better able to:

  • Distinguish between different types of thyroid cancers and identify appropriate therapies for their management
  • Plan for the use of precision medicine in thyroid cancer, including implementation of biomarker testing and use of novel targeted therapies
  • Evaluate the clinical trial data for novel targeted therapies for thyroid cancer and translate it into clinical practice
Faculty & Disclosures
Dr Antonio Matrone

University of Pisa, Pisa, Italy

Antonio Matrone, MD, PhD, is a postdoctoral researcher at the Endocrine Unit of the Department of Clinical and Translational Sciences at the University of Pisa, Italy, a position he has held since 2018.

Dr Matrone attended the University of Naples, Italy and obtained his MD in 2006, magna cum laude. He attended as a resident fellow at the Endocrine Unit of the University of Pisa and completed a speciality degree in endocrinology in 2012. From 2012 to 2014, he attended as a research fellow in endocrinology, focusing his activity on thyroid cancer in the thyroid oncology group, supervised by Professor Rossella Elisei. In 2018, Dr Matrone completed his PhD in clinical and translational sciences at the University of Pisa, magna cum laude. read more

He was awarded the Best Poster Award at several national congresses; the Young Investigators’ Prize of the European Thyroid Association (ETA) in 2016 for the best clinical paper in researchers aged <35 years; and the ENDO Experience Junior Faculty Travel Award of the Endocrine Society for ‘outstanding, high-scoring abstracts that were accepted for presentation at ENDO’ at the Endocrine Society Congress in 2020.

He is involved in all aspects of the management of patients with thyroid cancer, from molecular biology to clinical management, with special expertise in the management of advanced thyroid cancer with new multi-kinase and selective inhibitor therapies. He has been a sub-investigator on several clinical studies involving patients with advanced, progressive thyroid cancer.

Dr Antonio Matrone discloses Advisory board and panel fees from Eli Lilly.
Dr Lori Wirth

Massachusetts General Hospital, Boston, MA, USA

Dr Lori Wirth is The Elizabeth and Michael Ruane Chair of Endocrine Oncology and Medical Director of Massachusetts General Hospital’s Center for Head and Neck Cancers. She is an Associate Professor in Medicine at Harvard Medical School. In addition to overseeing the Center for Head and Neck Cancers, Dr Wirth co-directs Massachusetts General/Massachusetts Eye and Ear’s Advanced Thyroid Cancer Clinic. read more

Dr Wirth received her BA from Brown University and her MD from Columbia’s College of Physicians and Surgeons. She trained at New York Presbyterian Hospital and Dana-Farber/Harvard Cancer Center.

Dr Wirth is an international authority in advanced thyroid cancer and head and neck oncology. Her research focuses on clinical trials and leveraging translational data to maximize the impact of trial outcomes.

Dr Wirth has served as Chairperson of the International Thyroid Oncology Group, and sits on a number of national and international oncology committees, including the National Comprehensive Cancer Network (NCCN)’s Thyroid Committee and the American Board of Internal Medicine (ABIM)’s Medical Oncology Exam Committee.

Dr Lori Wirth discloses Advisory board and panel fees from Bayer HealthCare Pharmaceuticals, Blueprint Medicines, Eli Lilly and Exelixis. Consultancy fees from Eisai.
Dr Peter Sadow

Massachusetts General Hospital, Boston, MA, USA

Dr Peter Sadow is Director of Head and Neck Pathology at Massachusetts General Hospital and Massachusetts Eye and Ear, and the primary consultant in endocrine pathology. He has worked at Massachusetts General Hospital for nearly 15 years and is also Associate Professor at Harvard Medical School. read more

He completed his undergraduate degree in Biology and Egyptian History and Archaeology at Johns Hopkins University, then undertook a combined MD/PhD programme at the University of Chicago. His doctoral thesis utilized transgenic mouse models with altered thyroid hormone response genes in order to understand and advance our knowledge of the effects of thyroid hormone on human physiology.

His clinical and research interests have continued in endocrine pathology, studying the mechanisms of endocrine carcinogenesis through translational studies involving the proteomics and genomics of endocrine neoplasia, primarily of the thyroid and adrenal glands.

In addition to his clinical and research interests, Dr Sadow has prominent teaching roles at Massachusetts General, Harvard Medical School, and in Harvard Continuing Medical Education courses.

Dr Peter Sadow discloses Consultancy fees from Bayer and Veracyte.
Ms Tara Hurley

The Royal Marsden NHS Foundation Trust, Sutton, UK

Tara Hurley has been a UK-registered nurse since 2006, specializing in oncology and palliative care. Ms Hurley began her research career in 2010 working in the world-renowned oncology centre, The Royal Marsden NHS Foundation Trust, and is currently a Lead Research Nurse. Ms Hurley leads a clinical team of nurses and biological specimen co-ordinators to provide clinical trial options for patients with diagnoses of head, neck and thyroid cancer, as well as other solid tumours.

Ms Hurley’s primary motivation in her role is the safety and well-being of all trial participants and affording treatment options to those who have limited trajectories of care available. She feels her knowledge in caring for patients within clinical trials has now carried over into the way she treats and cares for patients in daily clinical practice.

Ms Tara Hurley has no interests/relationships or affiliations to disclose in relation to this activity.
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This Activity Is Funded By:

This educational activity is supported by independent medical education grants from Eli Lilly and Bayer.
This activity is jointly provided by USF Health and touchIME.

The information provided by this CME activity is for continuing education purposes only and is not meant to substitute for the independent medical/clinical judgment of a healthcare provider relative to diagnostic and treatment options of a specific patient’s medical condition.

USF is an Equal Opportunity / Affirmative Action / Equal Access Institution.

USF Health is accredited by the Accreditation Council for Continuing Medical Education, the American Nurses Credentialing Center and the Accreditation Council for Pharmacy Education to provide continuing education to healthcare professionals. As an accredited provider, USF Health is required to disclose personal information to relevant accredited bodies that certify CE to process credits/contact hours, comply with reporting requirements, and for internal recordkeeping and regulatory purposes. USF Health does not share or sell any individual’s contact information or unique identifiers to any commercial supporter, advertiser, or third party without the specific permission of the individual.

Unapproved products or unapproved uses of approved products may be discussed by the faculty; these situations may reflect the approval status in one or more jurisdictions. The presenting faculty have been advised by touchIME and USF Health to ensure that they disclose any such references made to unlabelled or unapproved use. No endorsement by touchIME or USF Health of any unapproved products or unapproved uses is either made or implied by mention of these products or uses in touchIME or USF Health activities. touchIME and USF Health accept no responsibility for errors or omissions.

This content is intended for healthcare professionals.

Date of original release: 29 November 2021. Date credits expire: 29 November 2023.

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Question 1/4
What information about FTC would you give to newly-diagnosed patients when explaining the epidemiology of the disease?

FTC, follicular thyroid cancer; PTC, papillary thyroid cancer.
 Correct

Follicular cell-derived thyroid cancers, which comprise 95% of all thyroid malignancies, are subsumed under the umbrella categories of PTC, FTC (including Hürtle cell cancer, a rare variant of FTC), poorly differentiated thyroid cancer and undifferentiated (anaplastic) thyroid cancer. The most common tumour entity is PTC (80–85%), followed by FTC (10–15%), poorly differentiated thyroid cancer and undifferentiated thyroid cancer (<2% each). These percentages vary at a population level depending on the presence or absence of environmental factors, such as iodine supply, ionizing radiation and diet.

Abbreviations
FTC, follicular thyroid cancer; PTC, papillary thyroid cancer.

Reference
Dralle H, et al. Nat Rev Dis Primers. 2015;1:15077.

Question 2/4
Your patient is a 59-year-old woman with unresectable metastatic MTC. She has a RET M918T mutation and has received one, non-TKI-based, prior systemic therapy for MTC. You decide to initiate vandetinib (a multikinase inhibitor) therapy. Your patient asks you what side effects to expect when taking the drug. How would you respond?

MTC, medullary thyroid cancer; TKI, tyrosine kinase inhibitor.
 Correct

Clinical trial experience with vandetinib has demonstrated that in patients with unresectable locally advanced or metastatic MTC treated with vandetinib 300 mg (n=231) or placebo (n=99) and exposed to the drug for a median of 607 days, the most commonly reported adverse events were diarrhoea/colitis, rash, acneiform dermatitis, hypertension, nausea, headache, upper respiratory tract infection, decreased appetite and abdominal pain. Dose interruption occurred in 47% of patients, and dose reduction in 36%. Adverse reactions led to study treatment discontinuation in 12% of patients receiving vandetanib, and in 3% receiving placebo.

Abbreviation
MTC, medullary thyroid cancer.

Reference
Caprelsa (vandetinib) Prescribing Information. 2020. Available at: www.caprelsa.com/files/caprelsa-pi.pdf

Question 3/4
Your patient is a 49-year-old man with PTC, whose disease has locally advanced despite chemotherapy. You decide to test him for a number of biomarkers, including NTRK gene fusions. Assuming all are available, which of these methods would you select, based on precision, efficiency and ease-of-use, for NTRK fusion detection?

PTC, papillary thyroid cancer; RT-PCR, reverse-transcriptase polymerase chain reaction.
 Correct

NGS provides a precise method to detect NTRK gene fusions, with high sensitivity and specificity compared with other testing methods.1 An advantage of NGS is that multiple oncogenic events in addition to NTRK gene fusions can be identified from a single tumour sample.1

IHC enables detection of TRK overexpression as a surrogate for the presence of an NTRK gene fusion and provides a time-efficient and tissue-efficient technique that may be used for routine screening. Positive IHC results must be followed with confirmatory testing using a molecular method to verify the presence of a fusion, as overexpression of wild-type TRK proteins may also be detected.1

Break-apart FISH is a well-established method for detecting clinically relevant gene fusion events and is of value in tumours with a high prevalence of NTRK gene fusions involving recurrent fusions. As FISH is largely limited to the detection of a single gene fusion, a separate break-apart FISH probe is required for each of the three NTRK genes. Furthermore, the 5’ gene fusion partner will not be identified. False negatives may result if the deletion is small enough to leave enough of the complementary regions for hybridization of both FISH probes, or if there is a complex FISH pattern with numerous nuclei showing atypical doublet fusion signals and only a few nuclei with split signals.1 Indeed, in one study, ETV6 FISH was associated with a 36% false negative rate.2

RT-PCR provides an alternative or complementary approach to FISH, detecting NTRK gene fusions using primers in the coding sequence of the 5’ fusion partner and the NTRK kinase domain. A disadvantage of RT-PCR is that the large number of possible 5’ fusion partners may make a comprehensive multiplex RT-PCR assay challenging.1

Abbreviations
FISH, fluorescence in situ hybridization; IHC, immunohistochemistry; NGS, next-generation sequencing; RT-PCR, reverse-transcriptase polymerase chain reaction; TRK, tyrosine receptor kinase.

References

  1. Penault-Llorca F, et al. J Clin Pathol. 2019;72:460–7.
  2. Davis JL, et al. Am J Surg Pathol. 2019;43:435–45.
Question 4/4
Your patient is a 70-year-old man with metastatic anaplastic thyroid cancer harbouring an NTRK1 gene fusion. He has had surgery, radiotherapy and three prior systemic therapies. You decide to initiate larotrectinib therapy in this patient. Based on the latest published results, what will you tell him about the efficacy of the drug?
 Correct

In a pooled analysis of two larotrectinib clinical trials (NCT02122913 and NCT02576431) involving adult and paediatric patients with locally advanced or metastatic thyroid cancer harbouring an NTRK gene fusion, 28 patients were included: 19 papillary, 7 anaplastic and 2 follicular. Twelve (43%) patients had an NTRK1 fusion and 16 (57%) had an NTRK3 fusion. All had received prior treatment; 11 (44%) patients had received ≥3 prior systemic therapies.

ORR was 75%, including 29% for patients with anaplastic disease. Duration of response ranged from 1.9+ to 41.0+ months. Median PFS was not reached and the 12-month PFS rate was 81%.

Abbreviations
ORR, objective response rate; PFS, progression-free survival.

Reference
Cabanillas M, et al. Ann Oncol. 2020:31(Suppl. 4):S1026–33.

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