Endocrine Oncology CME ACCREDITED Watch Time: 35 mins

touchEXPERT OPINIONS Optimizing the management of gastroenteropancreatic neuroendocrine tumours

Watch leading experts explore how recent scientific and clinical advances may optimize the medical management of gastroenteropancreatic neuroendocrine tumours (GEP-NETs) in 2021, and beyond.

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Prof. Jonathan R Strosberg
Moffitt Cancer Center, Tampa, FL, USA
Reviewing the evidence base for GEP-NETs: What is new in 2021?

Prof. Jonathan R Strosberg, who leads the NET Division at Moffitt Cancer Center, Tampa, FL, USA, summarizes the scientific and clinical evidence for GEP-NET treatment strategies in 2021.

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Interview Questions

In this interview Prof. Strosberg answers the following questions:

  • What is the current treatment landscape in GEP-NETs?
  • How are advances in our understanding of the molecular pathology of GEP-NETs shaping future treatment prospects?
  • What treatment options are on the horizon for GEP-NETs?
  • How safe and effective are emerging treatment options in GEP-NETs?
About Prof. Jonathan R Strosberg

Prof. Jonathan Strosberg is an Associate Professor at the Moffitt Cancer Center, specializing in the management of neuroendocrine malignancies. He is a graduate of Harvard University and Cornell University Medical College. He completed his fellowship at the Moffitt Cancer Center. He now leads the NET division at Moffitt and heads the GI department research programme. read more

Prof. Strosberg has published over 150 articles and book chapters on the diagnosis and management of neuroendocrine malignancies, including first-author publications in the New England Journal of Medicine, Journal of Clinical Oncology, Clinical Cancer Research, Annals of Oncology, Annals of Surgery, and Cancer. He has authored 12 articles for UptoDate. He is Vice Chair of the North American Neuroendocrine Tumor Society (NANETS), serves on the neuroendocrine guidelines committee of the National Comprehensive Cancer Network (NCCN) and on the neuroendocrine task force of the National Cancer Institute (NCI), and co-chairs the Neuroendocrine Tumor section of Southwest Oncology Group (SWOG).

Prof. Jonathan R Strosberg discloses: Consultancy fees from Novartis. Grants/research support fees from Novartis. Speaker fees from Ipsen.

 
Prof. Thorvardur R Halfdanarson
Mayo Clinic School of Medicine, Rochester, MN, USA
The impact of new data: Do we need to change our practice?

Thorvardur R Halfdanarson, Professor of Oncology at the Mayo Clinic School of Medicine, Rochester, MN, USA, explores the potential impact of new data on clinical practice relevant to the management of GEP-NETs.

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Interview Questions

In this interview Prof. Halfdanarson answers the following questions:

  • Can we improve on the clinical outcomes achieved with current treatment approaches in GEP-NETS?
  • What advances have been made in PRRT treatment for GEP-NETs?
  • What are we learning from real-world experience surrounding clinical management of GEP-NETs?
  • How do PRRT approaches compare with molecularly targeted therapies in terms of optimizing outcomes for patients with GEP-NETs?
  • What more is needed to optimize outcomes for our patients with GEP-NETs, particularly in terms of survivorship and quality of life?
About Prof. Thorvardur R Halfdanarson

Thorvardur Halfdanarson is a Professor of Oncology at the Mayo Clinic College of Medicine and Science, and a Consultant in Medical Oncology at the Mayo Clinic, Rochester, USA, where he specializes in GI oncology with a focus on neuroendocrine tumours (NETs). Prof. Halfdanarson is the Chair of the GI Tumor Group within Medical Oncology at the Mayo Clinic, the Co-Chair of the Colorectal Cancer Tumor Board and the Assistant Hematology/Oncology Fellowship Director. read more

He is a member of the National Comprehensive Cancer Network (NCCN) guidelines panel for NETs, the past chair of the Guidelines and Publications Committee, is on the Board of Directors of the North American Neuroendocrine Tumor Society (NANETS), and is a faculty member for the European Society of Medical Oncology (ESMO) for neuroendocrine and endocrine neoplasms and cancers of unknown primary origin.

Prof. Thorvardur R Halfdanarson discloses: Advisory board/panel fees from Advanced Accelerator Applications, Crinetics Pharmaceuticals, Curium Pharma, Ipsen, ITM Isotopen Technologien München AG and Novartis. Grants/research support fees from Advanced Accelerator Applications and Novartis.

 
Dr Diane Reidy-Lagunes
Memorial Sloan Kettering Cancer Center, New York, NY, USA
Progressive disease: How should we monitor and treat our patients?

Diane Reidy-Lagunes, medical oncologist at the Memorial Sloan Kettering Cancer Center, New York, USA, appraises the need for a multidisciplinary approach to treatment and monitoring, and highlights the latest strategies for progressive disease management.

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Interview Questions

In this interview Dr Reidy-Lagunes answers the following questions:

  • What requirements for multidisciplinary treatment and care are needed to optimize disease management?
  • How should we monitor our patients with GEP-NETs to better support clinical and quality of life outcomes?
  • How do we currently assess and define disease progression in GEP-NETS?
  • How should we manage patients in the event of disease progression in the first-line setting?
  • How might emerging treatment options impact clinical management following disease progression in future?
About Dr Diane Reidy-Lagunes

Dr Diane Reidy-Lagunes is a medical oncologist at the Memorial Sloan Kettering Cancer Center, New York, USA.

Dr Diane Reidy-Lagunes discloses: Advisory board/panel fees from Advanced Accelerator Applications, Chiasma Inc., ITM Isotopen Technologien München AG and OncoLogics. Grants/research support fees from Ipsen and Novartis.

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Overview & Learning Objectives
Overview

In this activity, experts in the field of gastroenteropancreatic neuroendocrine tumours (GEP-NETs) explore how recent scientific and clinical advances may optimize approaches to the medical management of GEP-NETs in 2021, and beyond.

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, gastro-oncologists, gastroenterologists, radiologists and endocrinologists involved in the management of gastroenteropancreatic neuroendocrine tumours.

Disclosures

USF Health adheres to The Standards for Integrity and Independence in Accredited Continuing Education in all of its continuing professional development activities. It is USF Health’s policy that all persons in a position to influence content in this activity disclose any financial relationship with an ineligible organization. USF Health has mitigated all conflicts of interest.

Faculty

Prof. Jonathan R Strosberg discloses: Consultancy fees from Novartis. Grants/research support fees from Novartis. Speaker fees from Ipsen.

Prof. Thorvardur R Halfdanarson discloses: Advisory board/panel fees from Advanced Accelerator Applications, Crinetics Pharmaceuticals, Curium Pharma, Ipsen, ITM Isotopen Technologien München AG and Novartis. Grants/research support fees from Advanced Accelerator Applications and Novartis.

Dr Diane Reidy-Lagunes discloses: Advisory board/panel fees from Advanced Accelerator Applications, Chiasma Inc., ITM Isotopen Technologien München AG and OncoLogics. Grants/research support fees from Ipsen and Novartis.

Content reviewer

Olivia Pane, PharmD, CDCES has no financial interests/relationships or affiliations in relation to this activity.

Touch Medical Director

Paul Taylor 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 0.75 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 0.75 Category 1 credit 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.

Date of original release: 12 August 2021. Date credits expire: 12 August 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:

  • Interpret the data supporting new and emerging treatment options to improve outcomes for patients with GEP-NETs
  • Analyse current guidelines for the therapeutic agents to treat GEP-NETs
  • Appraise the criteria for assessing disease progression in GEP-NETs, and how they impact treatment choice
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Question 1/5
A 38-year-old patient is diagnosed with a well-differentiated, grade 2, midgut NET. On SSTR-based PET/CT imaging, the tumour shows SSTR expression and clinically significant tumour burden, including extrahepatic involvement, and is not resectable. Following progression on treatment with an SSA, what might you consider next in the management of this patient?

CT, computerized tomography; Lu, lutetium; NET, neuroendocrine tumour; PET, positron emission tomography; PRRT, peptide receptor radionuclide therapy; SSA, somatostatin analogue; SSTR, somatostatin receptor.
Correct

PRRT with 177Lu-DOTATATE is indicated for the treatment of SSTR-positive GEP-NETs, including foregut, midgut and hindgut NETs in adults.1 The NCCN suggests SSA prior to PRRT, and highlights well-differentiated and SSTR-positive NET status as key patient eligibility criteria for PRRT.2 Higher somatostatin receptor expression as a predictor of better response to PRRT has been reported.3

GEP, gastroenteropancreatic; NCCN, National Comprehensive Cancer Network; NET, neuroendocrine tumour; PRRT, peptide receptor radionuclide therapy; SSA, somatostatin analogue; SSTR, somatostatin receptor.

References

  1. US Food and Drug Administration. Prescribing information: lutetium Lu 177 dotatate. Available at: https://hcp.lutathera.com/wp-content/uploads/2020/12/Lutathera_USPI-20200528-v2-1.pdf (accessed 28 July 2021).
  2. National Comprehensive Cancer Network. NCCN Guidelines Version 1.2021: Neuroendocrine and Adrenal Tumors [Discussion update in progress]. Available at: www.nccn.org/guidelines/guidelines-detail?category=1&id=1448 (accessed 28 July 2021).
  3. Uri I, Grozinsky-Glasberg S. Clin Diabetes Endocrinol. 2018;4:16.
Question 2/5
Which of the following mutations are reportedly associated with poorly-differentiated, high grade NECs?

NEC, neuroendocrine carcinoma.
Correct

Based on the WHO 2019 classification of tumours of the digestive system, neuroendocrine neoplasms are divided into NETs or NECs based on their molecular differences.1 Mutations in MEN1, DAXX and ATRX are common in well-differentiated NETs, particularly in those originating in the pancreas.2 NECs often have TP53 or RB1 mutations, are poorly differentiated, very aggressive and usually present at an advanced stage with a poor prognosis.2

NEC, neuroendocrine carcinoma; NET, neuroendocrine tumour; WHO, World Health Organization.

References

  1. Nagetegaal ID, et al. Histopathology. 2020;76:182–8.
  2. Maffacini A, Carpa A. Endocrine Rev. 2019;40:506–36.
Question 3/5
The Phase II TALENT trial assessed safety and efficacy of lenvatinib in patients with previously treated advanced grade 1–2 GEP-NETs with documented progression following treatment with targeted therapy (Pan-NET cohort) or SSAs (GI-NET cohort). Which of the following statements best summarizes the key finding from this trial?

GEP, gastroenteropancreatic; GI, gastrointestinal; NET, neuroendocrine tumour, Pan, pancreatic; SSA, somatostatin analogue.
Correct

The phase II TALENT trial reported an overall response rate of 29.9%: 44.2% (Pan-NET) and 16.4% (GI-NET). Median progression-free survival was not significantly different between cohorts at 15.6 (95% CI, 11.4–NR) and 15.7 (95% CI, 12.1–19.5) months for the Pan-NET and GI-NET cohorts, respectively.

CI, confidence interval; GI, gastrointestinal; NET, neuroendocrine tumour; NR, not reached; Pan, pancreatic.

Reference

Capdevila J, et al. J Clin Oncol. 2021;10:2304–12.

Question 4/5
When evaluating disease progression in a younger patient with an SSTR-positive GI-NET and liver metastases, which of the following would be your preferred imaging methodology?

CT, computerized tomography; 18F-FDG-PET, fluorodeoxyglucose (18F) positron emission tomography; GI, gastrointestinal; MRI, magnetic resonance imaging; NET, neuroendocrine tumour; SSTR, somatostatin receptor.
Correct

MRI is a sensitive methodology for the detection and follow-up of patients with liver metastases, with the additional benefit of avoiding radiation exposure in younger patients who require long-term serial imaging. Single-phase conventional CT scans are less sensitive than three-phase CT (arterial, venous and non-contrast). 18F-FDG-PETs are rarely useful in well-differentiated NETs. Fluoroscopy is not recommended for the follow up of GEP-NETs

CT, computerized tomography; 18F-FDG-PET, fluorodeoxyglucose (18F) positron emission tomography; GEP, gastroenteropancreatic; GI, gastrointestinal; MRI, magnetic resonance imaging; NET, neuroendocrine tumour.

Reference

Merino-Casabiel X, et al. Clin Transl Oncol. 2018;20:1522–8.

Question 5/5
When treating a patient with a well-differentiated midgut NET with liver-dominant unresectable metastases, who is symptomatic on treatment with SSAs, which of the following would be an appropriate treatment option?

NET, neuroendocrine tumour; SSA, somatostatin analogue.
Correct

The 2021 NCCN guidelines for Neuroendocrine and Adrenal Tumors recommend hepatic arterial embolization for well-differentiated midgut NETs with liver-dominant unresectable metastases in patients that are: symptomatic on an SSA or following another form of systemic therapy,
progressive on an SSA or following another form of systemic therapy or presenting with bulky liver disease.1

For the other suggested options: capecitabine/temozolomide is a treatment option in non-midgut GI, lung and Pan-NETs; sunitinib is a treatment option for advanced Pan-NETs; and surufatinib is currently under investigation and not yet FDA-approved for the treatment of GEP-NETs.2–6

FDA, Food and Drug Administration; GEP, gastroenteropancreatic; GI, gastrointestinal; NET, neuroendocrine tumour; NCCN, National Comprehensive Cancer Network; Pan, pancreatic; SSA, somatostatin analogue.

References

  1. National Comprehensive Cancer Network. NCCN Guidelines Version 1.2021: Neuroendocrine and Adrenal Tumors [Discussion update in progress]. Available at www.nccn.org/guidelines/guidelines-detail?category=1&id=1448 (accessed 28 July 2021).
  2. Uri I, Grozinsky-Glasberg S. Clin Diabetes Endocrinol. 2018;4:16.
  3. Pavel M, et al. Ann Oncol. 2020;31:844–60.
  4. Herrera-Martinez AD, et al. Drugs. 2019;79:21–42.
  5. Xu J, et al. Lancet Oncol. 2020;21:1489-99;
  6. Xu J, et al. Lancet Oncol. 2020;21:1500–12.
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