Radiation Oncology/Melanoma/Mucosal

Mucosal Melanoma

Overview

• Rare, approximately 1% of all melanoma
  • H&N sites ~50% of mucosal melanomas, anus/rectum ~25%, female genitalia ~20%
• No risk factors have been substantiated
• Staging
  • AJCC 7th ed (2010) established staging system (no AJCC staging previously)
  • Ballantyne staging (1970) for H&N locations
    • Stage I: disease confined to the primary site (~75%)
    • Stage II: regional lymph node metastasis (~18%)
    • Stage III: distant metastasis (~7%)
• Surgery with negative margins should be primary approach
• Role of RT is unclear; there appears to be benefit in terms of local control, though impact on survival is unclear
• Survival is poor:
  • 5-year OS nasal melanoma ~30%, oral melanoma ~10%, paranasal sinuses 0%
  • 5-year OS LN- 30% vs. LN+ 20%
• Fractionation schedule is also not well established. Based on radiobiology, hypofractionated regimens may be reasonable, but may be difficult to tolerate in H&N regions

General

• Princess Margaret; 1982 PMID 6181042 -- "Radiotherapy for mucosal melanomas." (Harwood AR, Int J Radiat Oncol Biol Phys. 1982 Jul;8(7):1121-6.)
  • Retrospective. 18 patients (H&N 12, anorectal 6). Literature review for combined 25 patients
  • Outcome: local control 44%; if failed to respond to RT, rapid death. Local control >=4 Gy/fx 86% vs. <4 Gy/fx 28%
  • Conclusion: For H&N, consider as primary treatment. For anorectal and vaginal, treatment palliative and should be considered alternative to radical surgery

Head & Neck

• University of Florida; 2008 (1974-2005) PMID 18376227 -- "Mucosal melanoma of the head and neck." (Wagner M, Am J Clin Oncol. 2008 Feb;31(1):43-8.)
  • Retrospective. 17 patients with primary H&N mucosal melanoma treated with RT. 13 patients surgery + RT, 4 definitive RT.
  • Outcome: LC surgery+RT 100% vs. definitive RT 25%. Regional control neck RT 89% vs. no RT 75% (NS); all 3 patients with neck mets treated with surgery + neck dissection + RT and all died within 6 months. 1-year/5-year LC 79%/79%, RC 83%/83%, LRC 63%/63%, DMFS 29%/24%, OS 53%/28%
  • Fractionation: no difference between QD and BID
  • Conclusion: Locoregional control relative high, but most patients fail in distant sites. Approximately quarter cured at 5 years

• Colorado; 2003 (1985-1998) PMID 12925346 -- "The role of postoperative adjuvant radiation therapy in the treatment of mucosal melanomas of the head and neck region." (Owens JM, Arch Otolaryngol Head Neck Surg. 2003 Aug;129(8):864-8.)
  • Retrospective. 48 patients, mucosal melanoma of H&N. Surgery alone 42%
  • Outcome: LRC surgery alone 55%, surgery + RT 83%; DM 50% vs 46%; 5-year OS 45% vs 29%
  • Conclusion: Addition of RT decreased rate of local failure, but didn't impact survival because of high rate of distant mets

• Institut Gustave-Roussy; 2005 (France)(1979-1999) PMID 15578718 -- "Postoperative radiotherapy for primary mucosal melanoma of the head and neck." (Temam S, Cancer. 2005 Jan 15;103(2):313-9.)
  • Retrospective. 69 patients, primary H&N mucosal melanoma (67% sinonasal, 28% oral). Surgery alone 43%, surgery + RT 57%
  • Outcome: LR 54%, DM 68%. 2-year OS 47%, 5-year OS 20%
  • Conclusion: Prognosis was poor; high rate of distant mets and low rate of local control. Post-op RT improved local control even for small tumors

• UCLA
  • 1995 PMID 7782202 -- "Mucosal melanoma of the nasal cavity and paranasal sinuses." (Kingdom TT, Head Neck. 1995 May-Jun;17(3):184-9.)
    • Retrospective. 13 patients, surgery alone 8 and surgery + RT 7.
    • Outcome: 2-year OS 67%, 5-year OS 20%. LR 85%, DM 31%
    • Conclusion: Those with postop RT appeared to do better with prolonged DFS and OS
  • 1994 (1955-1991) PMID 8302112 -- "Mucosal melanoma of the head and neck: the impact of local control on survival." (Lee SP, Laryngoscope. 1994 Feb;104(2):121-6.)
    • Retrospective. 35 patients, mucosal melanoma H&N. Primary therapy radical surgery 43%, local resection (31%), RT (17%), and systemic therapy (6%).
    • Outcome: Local recurrence 80%. Local salvage in 24%. Patients with local control significantly longer survival
    • Conclusion: Aggressive local therapy should be initiated at presentation

• Yale; 1976 PMID 1000466 -- "Radiation therapy of malignant melanoma: experience with high individual treatment doses." (Habermalz HJ, Cancer. 1976 Dec;38(6):2258-62.)
  • Retrospective. 54 melanoma lesions, 3 mucosal melanoma. 1 patient treated with 42/7, with local recurrence at 1 months. 1 patient treated with 48/8, with CR for at least 18 months. 1 patient with 66/11, CR at 8 months
  • Conclusion: Preliminary results, but RT may play a useful role

Review

• Multi-Institutional, Italy; 2008 PMID 17822915 -- "What is the role of radiotherapy in the treatment of mucosal melanoma of the head and neck?" (Krengli M, Crit Rev Oncol Hematol. 2008 Feb;65(2):121-8. Epub 2007 Sep 5.)
  • What is known: 1) Surgery continues to play a major role in the treatment strategy, 2) Radiotherapy might improve local control after non-radical resection, 3) Radiotherapy is the most effective treatment modality for unresectable disease
  • What is unclear: 1) Indications for radiotherapy after complete resection, 2) Elective nodal irradiation, 3) Total dose, 4) Fractionation, 5) Use of high LET radiation, 6) Use of chemotherapy and possibly new target therapy in adjuvant setting

• UCSD; 1997 PMID 9338460 -- "Malignant mucosal melanoma of the head and neck: review of the literature and report of 14 patients." (Manolidis S, Cancer. 1997 Oct 15;80(8):1373-86.)
  • Review of 14 cases, and review of literature >1000 cases

• Moffitt Cancer Center; 1993 PMID 8516612 -- "Role of radiotherapy in the primary management of mucosal melanoma of the head and neck." (Trotti A, Semin Surg Oncol. 1993 May-Jun;9(3):246-50.)

Carbon Ion

• Chiba; 2008 (1994-2004) PMID 19046826 -- "Mucosal Malignant Melanoma of the Head and Neck Treated by Carbon Ion Radiotherapy." (Yanagi T, Int J Radiat Oncol Biol Phys. 2008 Nov 27. [Epub ahead of print])
  • Prospective. 72 patients, mucosal melanoma of H&N. Dose 52.8 - 64 GyE in 16 fxs. Median F/U 4.1 years
  • Outcome: 5-year LC 84%, DSS 40%, OS 27%. Tumor volume (>=100 ml) most significant prognostic predictor
  • Toxicity: No late Grade 3 toxicity
  • Conclusion: Carbon ion RT safe and effective for mucosal melanoma. Overall survival comparable to surgery