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Which of the following has the greatest impact on your choice to use neoadjuvant treatment in melanoma?

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Treatment toxicity
   
Possible delay to/prevention of surgery
   
Potential impact on technical conduct of surgery
   
Other/none of these
   

Poll

How confident are you implementing adjuvant immunotherapies in patients with stage IIB/C melanoma?

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Very confident
   
Confident
   
Somewhat confident
   
Not confident
   

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Poll

In your experience, what is the incidence of recurrence in stage II melanoma?

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<20%
   
20-40%
   
40-60%
   
>60%
   
 
Expert Interviews
Dermatological Cancers, Immunotherapy CE/CME accredited

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Experts answer questions with in-depth advice on the current clinical landscape and how new therapies and guidance might impact regional clinical practice. Useful tips below will show how to navigate the activity. Close

Navigating treatment choices in high-risk early-stage melanoma

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Dr Tina Hieken is a fellowship-trained surgical oncologist and professor of surgery at the Mayo Clinic, Rochester, MN, USA, where she is also medical director for quality and accreditation for the Mayo Clinic Comprehensive Cancer Center. read more

Dr Hieken serves as chair for the American College of Surgeons Cancer Surgery Standards Program and on several national committees and editorial boards. Her research interests are translational and include applications of molecular signatures in cancer and cancer-risk prediction and prevention; functional characterization of the endogenous microbiomes in health and disease; neoadjuvant immunotherapy and drivers of immune response; and surgical innovation, including the application of technological advances and minimally invasive techniques to deliver patient-focused surgical oncology care. Her research funding includes awards from the Stand Up to Cancer/American Association for Cancer Research Catalyst Program, the Breast Cancer Research Foundation and National Cancer Institute.

Dr Tina J Hieken discloses: Grants/research support from Genentech and SkylineDx.

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Prof. Piotr Rutkowski is professor of surgical oncology at the Maria Sklodowska-Curie National Research Institute of Oncology in Warsaw, Poland. Prof. Rutkowski is head of the Department of Soft Tissue/Bone Sarcoma and Melanoma, and plenipotentiary of head director of the Institute for National Oncological Strategy and Clinical Trials. read more

Prof. Rutkowski has participated in several investigator-driven trials in melanoma and sarcoma. He is a reviewer for several international scientific journals, as well as a member of the editorial board of Annals of Surgical Oncology and European Journal of Surgical Oncology.

Prof. Rutkowski is an active member of the European Organisation for Research and Treatment of Cancer (EORTC) Melanoma Group and EORTC Soft Tissue and Bone Sarcoma Group. He has chaired the EORTC Board Local Treatment Subcommittee and Membership Committee. He is a member of several Polish and international scientific societies (president of Polish Oncological Society, board member of Polish Society Surgical Oncology, ex-member of the board of directors of the Connective Tissue Oncology Society, member of Membership Advisory Committee of the American Society of Clinical Oncology [ASCO], and member of the Global Curriculum Committee of the European Society for Medical Oncology [ESMO]).

Prof. Rutkowski has authored or co-authored over 500 scientific papers in Polish and international journals, and is co-author of national and international recommendations for sarcoma and melanoma. He works very closely with national patient advocacy groups for gastrointestinal stromal tumours (GIST)/sarcoma and melanoma, coordinating the Polish Sarcoma Group, and is chairman of the Melanoma Academy in Poland, president of the Council of Agency of Medical Research, and chair of the Task Group of Ministry of Health, Poland for National Oncological Strategy.

Prof. Piotr Rutkowski discloses: Advisory board or panel fees from Bristol Myers Squibb, Genesis Pharma, Medison Pharma and MSD.

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Dr Teresa Amaral is head of the Skin Cancer Clinical Trials Center and lecturer at Tübingen University in Tübingen, Germany, Porto University and Beira Interior University, Portugal. Dr Amaral has been responsible for the Skin Cancer Center biobank in Tübingen since 2018 and has been head of the Skin Cancer Clinical Trials Center in Tübingen since 2021. read more

Dr Amaral has been a board-certified specialist in internal medicine, haematology and oncology through the German Medical Association since 2021. Her research primarily focuses on predictive biomarkers for systemic therapy in advanced melanoma and prognostic and predictive biomarkers in early-stage melanoma.

Dr Amaral has served as the chair of the European Society for Medical Oncology (ESMO) Young Oncologists Committee, and is currently a member of the ESMO Melanoma and Other Skin Tumours Faculty. She is a subject editor for the guidelines on melanoma and other skin cancers. Dr Amaral has been chair of the ESMO Leadership Development Committee since January 2023 and serves as an ESMO Council Member. She is an author or co-author on over 50 papers in peer-reviewed journals, including European Journal of Cancer, Journal of Clinical Oncology, Nature Medicine and ESMO Open.

Dr Teresa Amaral discloses: Advisory board or panel fees from Delcath and Philogen. Consulting fees from Bristol Myers Squibb, CeCaVa, MedTrix, MSD, NeraCare, Novartis and Pierre Fabre. Grants/research support from Agenus, AstraZeneca, BioNTech, Bristol Myers Squibb, HUYA Bioscience, iFIT, Immunocore, IO Biotech, MSD, NeraCare, Novartis, Pascoe, Pfizer, Philogen, Regeneron, Roche, Sanofi and SkylineDx.

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  • A practice aid is available for this activity in the Toolkit
  • Downloads including slides are available for this activity in the Toolkit
Learning Objectives

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

  • Recognize various prognostic indicators for predicting high-risk recurrence in patients with early-stage melanoma and their impact on clinical decision-making
  • Evaluate the latest data on immuno-oncology therapy in the adjuvant setting for melanoma stages IIB/C and how advances may affect clinical practice
  • Interpret recent data for neoadjuvant therapy and the role of biomarkers in developing sequential treatment plans for patients with early-stage melanoma
Overview

In this activity, three leading experts on melanoma discuss the risk of recurrence in early-stage disease, data for adjuvant and neoadjuvant therapies, and emerging biomarkers for predicting recurrence and guiding treatment decisions.

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 and dermatologists involved in the management of melanoma.

USF Accreditation

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. The relevant relationships are listed below. All individuals not listed have no relevant financial relationships.

Faculty

Dr Tina J Hieken discloses: Grants/research support from Genentech and SkylineDx.

Prof. Piotr Rutkowski discloses: Advisory board or panel fees from Bristol Myers Squibb, Genesis Pharma, Medison Pharma and MSD.

Dr Teresa Amaral discloses: Advisory board or panel fees from Delcath and Philogen. Consulting fees from Bristol Myers Squibb, CeCaVa, MedTrix, MSD, NeraCare, Novartis and Pierre Fabre. Grants/research support from Agenus, AstraZeneca, BioNTech, Bristol Myers Squibb, HUYA Bioscience, iFIT, Immunocore, IO Biotech, MSD, NeraCare, Novartis, Pascoe, Pfizer, Philogen, Regeneron, Roche, Sanofi and SkylineDx.

Content reviewer

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

Touch Medical Contributors

Hannah Fisher 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.

Advanced Practice Providers

Physician Assistants may claim a maximum of 0.75 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.

Date of original release: 19 December 2024. Date credits expire: 19 December 2027.

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

EBAC® Accreditation

touchIME is an EBAC® accredited provider since 2023.

This programme is accredited by the European Board for Accreditation of Continuing Education for Health Professionals (EBAC®) for 0.75 hour of effective education time.

The Accreditation Council for Continuing Medical Education (ACCME®), and the Royal College of Physicians and Surgeons of Canada hold an agreement on mutual recognition on substantive equivalency of accreditation systems with EBAC®.

Through an agreement between the European Board for Accreditation of Continuing Education for Health Professionals and the American Medical Association (AMA), physicians may convert EBAC® CE credits to AMA PRA Category 1 CreditsTM. Information on the process to convert EBAC® credit to AMA credit can be found on the AMA website. Other health care professionals may obtain from the AMA a certificate of having participated in an activity eligible for conversion of credit to AMA PRA Category 1 CreditTM.

Faculty Disclosure Statement / Conflict of Interest Policy

In compliance with EBAC® guidelines, all speakers/ chairpersons participating in this programme have disclosed or indicated potential conflicts of interest which might cause a bias in the presentations. The Organizing Committee/Course Director is responsible for ensuring that all potential conflicts of interest relevant to the event have been mitigated and declared to the audience prior to the CME activities.

Requirements for Successful Completion

Certificates of Completion may be awarded upon successful completion of the post-test and evaluation form. If you have completed one hour or more of effective education through EBAC® accredited CE activities, please contact us at accreditation@touchime.org to receive your EBAC® CE credit certificate. EBAC® grants 1 CE credit for every hour of education completed.

Date of original release: 19 December 2024. Date credits expire: 19 December 2026.

Time to Complete: 45 minutes

If you have any questions regarding the EBAC® credits, please contact accreditation@touchime.org

This activity is CE/CME accredited

To obtain the CE/CME credit(s) from this activity, please complete this post-activity test.

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  • Select in the video player controls bar to choose subtitle language. Subtitles available in English, French, German, Italian, Spanish.
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  • Downloads including slides are available for this activity in the Toolkit

Topics covered in this activity

Dermatological Cancers / Immunotherapy
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touchEXPERT OPINIONS
Navigating treatment choices in high-risk early-stage melanoma
0.75 CE/CME credit

Question 1/5
Which of the following tumour factors may contribute to an elevated risk of recurrence in patients with stage IIB/C melanoma?

Various tumour factors can impact the likelihood of recurrence in patients with stage IIB/C melanoma. Evidence shows that a primary tumour with a Breslow depth >4.0 mm or Breslow depth >2.1 mm with ulceration may increase recurrence risk.1,2

While mitotic rate has been removed from the AJCC 8th edition staging criteria for melanoma, recent studies continue to report a fast mitotic rate as a risk factor for recurrence.1–4

Abbreviation

AJCC, American Joint Committee on Cancer.

References

  1. Dedeilia A, et al. Ann Surg Oncol. 2024;31:2713–26.
  2. Gershenwald JE, et al. CA Cancer J Clin. 2017;67:472–92.
  3. von Schuckmann LA, et al. JAMA Dermatol. 2019;155:688–93.
  4. Iqbal A, et al. J Am Acad Dermatol. 2023;89:154–5.
Question 2/5
Which of the following patients with stage IIB/C melanoma has the greatest number of characteristics associated with an increased risk of melanoma recurrence?

Several patient-specific factors may impact the outcomes of patients with melanoma.1 A recent cohort study of 1,931 patients found that men were more likely to have recurrence than women (HR 1.7 [95% CI: 1.19–2.43]).2 One study reported a higher risk of recurrence among patients >75 years vs 65–75 years of age.3 A history of comorbidities, such as congestive heart failure, diabetes with associated complications and chronic lung disease can contribute to an increased risk of recurrence.3

Abbreviations

CI, confidence interval; HR, hazard ratio.

References

  1. NCCN Clinical Practice Guidelines in Oncology. Melanoma: Cutaneous. Version 3.2024. Available at: NCCN.org (accessed 26 November 2024).
  2. Feigelson HS, et al. Cancer Med. 2019;8:4508–16.
  3. Jang S, et al. Dermatol Ther (Heidelb). 2020;10:985–99.
Question 3/5
Your patient is a 65-year-old male with stage IIB cutaneous melanoma of the thigh (BRAF wild type). He has undergone wide excision and SLNB, which has come back as negative. What would you do now?

SLNB, sentinel lymph node biopsy

According to the latest NCCN and ESMO guidelines, patients with stage IIB disease who are SLN negative should be considered for adjuvant therapy with a clinical trial, or immunotherapy with pembrolizumab or nivolumab, or observation.1,2 

Abbreviations

ESMO, European Society for Medical Oncology; NCCN, National Comprehensive Cancer Network; SLN, sentinel lymph node.

References

  1. NCCN Clinical Practice Guidelines in Oncology. Melanoma: Cutaneous. Version 3.2024. Available at: NCCN.org (accessed 26 November 2024).
  2. Amaral T, et al. Ann Oncol. 2024. doi: 10.1016/j.annonc.2024.11.006 (Online ahead of print).
Question 4/5
Which of the following statements best describes the latest outcomes from the adjuvant ICI trials of pembrolizumab vs placebo (KEYNOTE-716; 48-month data) and nivolumab vs placebo (CheckMate 76K; 36-month data) in patients with stage IIB/C melanoma?

DMFS, distant metastasis-free survival; ICI, immune checkpoint inhibitor; irAE, immune-related adverse event; PRFS2 progression-/RFS 2; RFS, recurrence-free survival.

In the KEYNOTE-716 trial, adjuvant pembrolizumab was compared with placebo.1 At 48 months, RFS was 71% with pembrolizumab and 58% with placebo; DMFS was 81% and 70%, respectively; and PRFS2 was 83% and 77%, respectively.2 No new safety signals were identified during pembrolizumab rechallenge or crossover.2

In the CheckMate 76K trial, patients received adjuvant nivolumab or placebo.3 At 36 months, RFS was 71% with nivolumab and 61% with placebo; DMFS was 79% and 74%, respectively; and PRFS2 was 87% and 85%, respectively.4 No new safety signals were identified since the primary analysis.4

Abbreviations

DMFS, distant metastasis-free survival; PRFS2 progression-/RFS 2; RFS, recurrence-free survival.

References

  1. Luke JJ, et al. Lancet. 2022;399:1718–29.
  2. Luke JJ, et al. Presented at: European Society for Medical Oncology Congress, Barcelona, Spain. 13–17 September 2024. Abstr 1078MO.
  3. Kirkwood JM, et al. Nat Med. 2023;29:2835–43.
  4. Long GV, et al. Presented at: European Society for Medical Oncology Congress, Barcelona, Spain. 13–17 September 2024. Abstr 1077MO.
Question 5/5
Which of the following biomarkers was found to correlate with improved RFS and OS following neoadjuvant therapy in the INMC study and is a potential surrogate endpoint for clinical trials?

CD, cluster of differentiation; ERK, extracellular signal-regulated kinases; IFN-γ, interferon gamma; INMC, International Neoadjuvant Melanoma Consortium; OS, overall survival; RFS, recurrence-free survival.

The 2021 INMC pooled analysis found that pathologic response to neoadjuvant immunotherapy corresponded with improved RFS and OS in patients with stage III melanoma.1 Pathologic response is considered a potential surrogate endpoint in patients with resectable melanoma.1–3

Studies of neoadjuvant ipilimumab + nivolumab found that high baseline IFN-γ was associated with significantly prolonged efficacy outcomes,4,5 and reported higher CD8+ T-cell transcripts in patients with pathologic response.6,7 Findings regarding an association between lower phosphorylation of ERK and pathologic complete response have been mixed.8,9 Further research is needed to establish validated biomarkers in this setting.7

Abbreviations

CD, cluster of differentiation; ERK, extracellular signal-regulated kinases DMFS, distant metastasis-free survival; IFN-γ, interferon gamma; INMC, International Neoadjuvant Melanoma Consortium; OS, overall survival; RFS, recurrence-free survival.

References

  1. Menzies AM, et al. Nat Med. 2021;27:301–9.
  2. van Akkooi ACJ, et al. Ann Surg Oncol. 2022;29:3694–708.
  3. Pavlick AC, et al. J Immunother Cancer. 2023;11:e006947.
  4. Rozeman EA, et al. Ann Oncol. 2019;30(Suppl 5):Abstr LBA75.
  5. Rutkowski P, Mandala MP. Eur J Surg Oncol. 2024;50:107969.
  6. Amaria RN, et al. Nat Med. 2018;24:1649–54. 
  7. Błoński PJ, et al. Biomedicines. 2024;12:669.
  8. Amaria RN, et al. Lancet Oncol. 2018;19:181–93.
  9. Long GV, et al. Lancet Oncol. 2019;20:961–71.
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