Version 3.2021, 04/27/21 © 2021 National Comprehensive Cancer Network® (NCCN®), All rights reserved. NCCN Guidelines® and this illustration may not be reproduced in any form without the express written permission of NCCN.
Note: All recommendations are category 2A unless otherwise indicated.
Clinical Trials: NCCN believes that the best management of any patient with cancer is in a clinical trial. Participation in clinical trials is especially encouraged.
Version 3.2021, 04/27/21 © 2021 National Comprehensive Cancer Network® (NCCN®), All rights reserved. NCCN Guidelines® and this illustration may not be reproduced in any form without the express written permission of NCCN.
Note: All recommendations are category 2A unless otherwise indicated.
Clinical Trials: NCCN believes that the best management of any patient with cancer is in a clinical trial. Participation in clinical trials is especially encouraged.
Mucosal Melanoma
MM-2
h See Principles of Surgery (SURG-A).
i See Principles of Radiation Therapy (MM-A).
j See Systemic Therapy for Metastatic or Unresectable Disease (page ME-I) from the NCCN Guidelines for Cutaneous Melanoma.
k While adjuvant systemic therapy may be used for mucosal melanoma, the data to support its use are far thinner than for cutaneous melanoma. Options may include nivolumab (category 2B) or cisplatin/temozolomide (category 2B). See Discussion.
PRIMARY TREATMENT ADJUVANT TREATMENT
Sinus or nasal cavity mucosal melanoma
T3,N0 Resection of primaryh orClinical trial
Strongly consider postoperative RTi to primary site
±Systemic therapy (category 2B)k
T3–T4a,N1
Resection + neck dissection of positive neckh
orClinical trial
Postoperative RTi to primary site and neck±
Systemic therapy (category 2B)k T4a,N0
T4b,N0
T4b,N1
Resectionh orClinical trial
Postoperative RTi to primary site
±Systemic therapy (category 2B)k
Clinical trial (preferred) or Primary RTi
or Systemic therapyj
Clinical trial (preferred) or Best supportive care or Primary RTi
or Systemic therapyj
Follow-up (See FOLL-A)
Recurrent or persistent disease, see NCCN Guidelines for Cutaneous Melanoma See Post Systemic Therapy/RT or
RT Neck Evaluation (FOLL-A, 2 of 2)
Version 3.2021, 04/27/21 © 2021 National Comprehensive Cancer Network® (NCCN®), All rights reserved. NCCN Guidelines® and this illustration may not be reproduced in any form without the express written permission of NCCN.
Note: All recommendations are category 2A unless otherwise indicated.
Clinical Trials: NCCN believes that the best management of any patient with cancer is in a clinical trial. Participation in clinical trials is especially encouraged.
Mucosal Melanoma
MM-3
h See Principles of Surgery (SURG-A).
i See Principles of Radiation Therapy (MM-A).
j See Systemic Therapy for Metastatic or Unresectable Disease (page ME-I) from the NCCN Guidelines for Cutaneous Melanoma.
k While adjuvant systemic therapy may be used for mucosal melanoma, the data to support its use are far thinner than for cutaneous melanoma. Options may include nivolumab (category 2B) or cisplatin/temozolomide (category 2B). See Discussion.
Oral cavity, oropharynx, larynx, or hypopharynx mucosal melanoma
PRIMARY TREATMENT ADJUVANT
TREATMENT FOLLOW-UP
Resectionh T3,N0
Strongly consider postoperative RTi
±Systemic therapy (category 2B)k
T3,N1 or
T4a,N0–1 Resection
± neck dissectionh Postoperative RTi
±Systemic therapy (category 2B)k
T4b,N0
T4b,N1
Clinical trial (preferred) orPrimary RTi
and/or
Systemic therapyj
Clinical trial (preferred) or Best supportive care orPrimary RTi
or Systemic therapyj
Follow-up (See FOLL-A)
Recurrent or
persistent disease, see NCCN Guidelines for Cutaneous Melanoma See Post Systemic Therapy/RT or
RT Neck Evaluation (FOLL-A, 2 of 2)
Version 3.2021, 04/27/21 © 2021 National Comprehensive Cancer Network® (NCCN®), All rights reserved. NCCN Guidelines® and this illustration may not be reproduced in any form without the express written permission of NCCN.
Note: All recommendations are category 2A unless otherwise indicated.
Clinical Trials: NCCN believes that the best management of any patient with cancer is in a clinical trial. Participation in clinical trials is especially encouraged.
Mucosal Melanoma
MM-4
h See Principles of Surgery (SURG-A).
i See Principles of Radiation Therapy (MM-A).
l High-risk: adverse features: >2 nodes, single node >3 cm, extranodal extension, recurrence in nodal basin after previous surgery.
PRIMARY THERAPY FOR OCCULT PRIMARY- MELANOMA (Also see NCCN Guidelines for Occult Primary)
Nodal basin Nodal dissectionh ± RT to nodal basin for
high-risk featuresi,l ± Adjuvant systemic therapy, per
NCCN Guidelines for Cutaneous Melanoma
Version 3.2021, 04/27/21 © 2021 National Comprehensive Cancer Network® (NCCN®), All rights reserved. NCCN Guidelines® and this illustration may not be reproduced in any form without the express written permission of NCCN.
Note: All recommendations are category 2A unless otherwise indicated.
Clinical Trials: NCCN believes that the best management of any patient with cancer is in a clinical trial. Participation in clinical trials is especially encouraged.
Mucosal Melanoma
MM-A
1 See Principles of Radiation Techniques (RAD-A) and Discussion.
2 Recent studies suggest that increased toxicity may occur when RT is used in combination with BRAF inhibitors. [Anker CJ, Grossmann KF, Atkins MB, et al. Avoiding severe toxicity from combined BRAF inhibitor and radiation treatment: Consensus guidelines from the Eastern Cooperative Oncology Group (ECOG). Int J Radiat Oncol Biol Phys 2016;95:632-646.]
3 Optional dose schedules include 48–50 Gy (2.4–3.0 Gy/fraction) and 30–36 Gy (6 Gy/fraction). (Burmeister BH, Henderson MA, Ainslie J, et al. Adjuvant radiotherapy versus observation alone for patients at risk of lymph-node field relapse after therapeutic lymphadenectomy for melanoma: a randomised trial. Lancet Oncol
2012;13:589-597; Ballo MT, Bonnen MD, Garden AS, et al. Adjuvant irradiation for cervical node metastases from melanoma. Cancer 2003;97:1789-1796; and Moreno MA, Roberts DB, Kupferman ME, et al. Mucosal melanoma of the nose and paranasal sinuses, a contemporary experience from the M. D. Anderson Cancer Center.
Cancer 2010;116:2215-2223).
PRINCIPLES OF RADIATION THERAPY1,2 DEFINITIVE:
RT Alone (unresectable locally advanced melanoma):
• PTV:
High risk: Primary tumor and involved lymph nodes [this includes possible local subclinical infiltration at the primary site and at the high-risk-level lymph node(s)]
◊66 Gy (2.2 Gy/fraction) to 70 Gy (2.0 Gy/fraction) daily Monday–Friday in 6–7 weeks
Low to intermediate risk: Sites suspected of subclinical spread
◊44–50 Gy (2.0 Gy/fraction) to 54–63 Gy (1.6–1.8 Gy/fraction)
• Palliative RT doses and schedules may be considered.
• Optional dosing schedules may be considered.3 POSTOPERATIVE:
RT: • Preferred interval between resection and postoperative RT is <6 weeks.
• PTV
High risk: adverse features >2 nodes, single node >3 cm, extranodal extension, recurrence in nodal basin after previous surgery2
◊60–66 Gy (2.0 Gy/fraction; daily Monday–Friday) in 6–6.5 weeks
Low to intermediate risk: sites of suspected subclinical spread
◊44–50 Gy (2.0 Gy/fraction) to 54–63 Gy (1.6–1.8 Gy/fraction)
• Optional dosing schedules may be considered.3
Either IMRT or 3D conformal RT is recommended. Proton therapy can be considered when normal tissue constraints cannot be met by photon-based therapy.