Vol 15, No 6 (2019)
Review paper
Published online: 2020-01-10

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The role of radiotherapy in melanoma

Mateusz Spałek, Anna M. Czarnecka
Oncol Clin Pract 2019;15(6):310-319.


The role of radiotherapy (RT) in the treatment of melanoma is constantly evolving. Although melanoma is considered
a radioresistant tumour with great potential for repairing sub-lethal damage, RT is an important component
of treatment. Indications for sole or adjuvant radiotherapy of the primary lesion are limited and include desmoplastic
melanoma, the presence of satellite lesions and/or in-transit metastases, the presence of melanoma cells
in blood or lymphatic vessels, infiltration of nerve trunks, recurrence after previous surgery, and locally advanced
melanomas of the head and neck region, especially inoperable. In the past, the most common indication for
radiotherapy in melanoma was adjuvant treatment after lymphadenectomy in patients with risk factors for nodal
recurrence (large metastasis diameter, multiple nodes involved, extracapsular extension). Adjuvant radiotherapy
after lymphadenectomy has been shown to almost double the local control of the disease, but it does not affect
patient survival and may also lead to significant toxicity. Nevertheless, currently the recommended approach is
systemic adjuvant treatment (anti-PD-1 immunotherapy with pembrolizumab or nivolumab and, in the presence of
BRAF mutation, BRAF/MEK inhibitors), and RT should be reserved for situations in which there are contraindications
to other adjuvant treatment. Stereotactic techniques, including radiosurgery of brain metastases, are becoming
more widely used. RT could be a definitive treatment for a limited number of metastases or in cases of limited
progression on systemic treatment. The effectiveness of RT can be increased by combining with hyperthermia. An
increasing number of reports suggest great benefit from the combination of RT with immunotherapy. At present,
there is no convincing evidence supporting the combination of RT with molecularly targeted treatment, and according
to emerging data on the toxicity of such a combination it should be used with caution.

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  1. Delaney G, Barton M, Jacob S. Estimation of an optimal radiotherapy utilization rate for melanoma: a review of the evidence. Cancer. 2004; 100(6): 1293–1301.
  2. Radiation biology of malignant melanoma. PubMed — NCBI [Internet]. [cited 2019 Sep 9]. Available from: https://www.ncbi.nlm.nih.gov/pubmed/3010642.
  3. Bentzen SM, Overgaard J, Thames HD, et al. Clinical radiobiology of malignant melanoma. Radiother Oncol. 1989; 16(3): 169–182.
  4. Chang DT, Amdur RJ, Morris CG, et al. Adjuvant radiotherapy for cutaneous melanoma: comparing hypofractionation to conventional fractionation. Int J Radiat Oncol Biol Phys. 2006; 66(4): 1051–1055.
  5. van Leeuwen CM, Oei AL, Crezee J, et al. The alfa and beta of tumours: a review of parameters of the linear-quadratic model, derived from clinical radiotherapy studies. Radiat Oncol. 2018; 13(1): 96.
  6. Hedblad MA, Mallbris L. Grenz ray treatment of lentigo maligna and early lentigo maligna melanoma. J Am Acad Dermatol. 2012; 67(1): 60–68.
  7. Varey AHR, Goumas C, Hong AM, et al. Neurotropic melanoma: an analysis of the clinicopathological features, management strategies and survival outcomes for 671 patients treated at a tertiary referral center. Mod Pathol. 2017; 30(11): 1538–1550.
  8. Radiotherapy influences local control in patients with desmoplastic melanoma. PubMed — NCBI [Internet]. [cited 2019 Sep 9]. Available from: https://www.ncbi.nlm.nih.gov/pubmed/24142775.
  9. Radiotherapy for cutaneous malignant melanoma: rationale and indications. PubMed — NCBI [Internet]. [cited 2019 Sep 9]. Available from: https://www.ncbi.nlm.nih.gov/pubmed/14768409.
  10. Guadagnolo BA, Prieto V, Weber R, et al. The role of adjuvant radiotherapy in the local management of desmoplastic melanoma. Cancer. 2014; 120(9): 1361–1368.
  11. Chang AE, Karnell LH, Menck HR. The National Cancer Data Base report on cutaneous and noncutaneous melanoma: a summary of 84,836 cases from the past decade. The American College of Surgeons Commission on Cancer and the American Cancer Society. Cancer. 1998; 83(8): 1664–1678, doi: 10.1002/(sici)1097-0142(19981015)83:8<1664::aid-cncr23>3.0.co;2-g.
  12. Benlyazid A, Thariat J, Temam S, et al. Postoperative radiotherapy in head and neck mucosal melanoma: a GETTEC study. Arch Otolaryngol Head Neck Surg. 2010; 136(12): 1219–1225.
  13. Kirschner AN, Kidd EA, Dewees T, et al. Treatment approach and outcomes of vaginal melanoma. Int J Gynecol Cancer. 2013; 23(8): 1484–1489.
  14. 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(6): 589–597.
  15. Henderson MA, Burmeister BH, Ainslie J, et al. Adjuvant lymph-node field radiotherapy versus observation only in patients with melanoma at high risk of further lymph-node field relapse after lymphadenectomy (ANZMTG 01.02/TROG 02.01): 6-year follow-up of a phase 3, randomised controlled trial. Lancet Oncol. 2015; 16(9): 1049–1060.
  16. Ballo MT, Garden AS, Myers JN, et al. Melanoma metastatic to cervical lymph nodes: Can radiotherapy replace formal dissection after local excision of nodal disease? Head Neck. 2005; 27(8): 718–721.
  17. Cheung P. Stereotactic body radiotherapy for oligoprogressive cancer. Br J Radiol. 2016; 89(1066): 20160251.
  18. Overgaard J, Gonzalez Gonzalez D, Hulshof MC, et al. Randomised trial of hyperthermia as adjuvant to radiotherapy for recurrent or metastatic malignant melanoma. European Society for Hyperthermic Oncology. Lancet. 1995; 345(8949): 540–543.
  19. Rogers SJ, Puric E, Eberle B, et al. Radiotherapy for Melanoma: More than DNA Damage. Dermatol Res Pract. 2019: 9435389.
  20. Seegenschmiedt MH, Keilholz L, Altendorf-Hofmann A, et al. Palliative radiotherapy for recurrent and metastatic malignant melanoma: prognostic factors for tumor response and long-term outcome: a 20-year experience. Int J Radiat Oncol Biol Phys. 1999; 44(3): 607–618.
  21. Rutkowski P, Kiprian D, Dudzisz-Śledź M, et al. Postępowanie w przerzutach czerniaka do mózgowia. Onkol Prakt Klin Edu. 2019; 5: 54–65.
  22. Laufer I, Iorgulescu JB, Chapman T, et al. Local disease control for spinal metastases following "separation surgery" and adjuvant hypofractionated or high-dose single-fraction stereotactic radiosurgery: outcome analysis in 186 patients. J Neurosurg Spine. 2013; 18(3): 207–214.
  23. Laufer I, Rubin DG, Lis E, et al. The NOMS framework: approach to the treatment of spinal metastatic tumors. Oncologist. 2013; 18(6): 744–751.
  24. Stereotactic radiosurgery: A new paradigm for melanoma and renal cell carcinoma spine metastases. Journal of Clinical Oncology [Internet]. [cited 2019 Sep 9]. Available from: https://ascopubs.org/doi/abs/10.1200/jco.2010.28.15_suppl.2030.
  25. Ugurel S, Thirumaran RK, Bloethner S, et al. B-RAF and N-RAS mutations are preserved during short time in vitro propagation and differentially impact prognosis. PLoS One. 2007; 2(2): e236.
  26. Ahmed KA, Abuodeh YA, Echevarria MI, et al. Clinical outcomes of melanoma brain metastases treated with stereotactic radiosurgery and anti-PD-1 therapy, anti-CTLA-4 therapy, BRAF/MEK inhibitors, BRAF inhibitor, or conventional chemotherapy. Ann Oncol. 2016; 27(12): 2288–2294.
  27. Patel KR, Chowdhary M, Switchenko JM, et al. BRAF inhibitor and stereotactic radiosurgery is associated with an increased risk of radiation necrosis. Melanoma Res. 2016; 26(4): 387–394.
  28. Minniti G, Scaringi C, Paolini S, et al. Single-Fraction Versus Multifraction (3 × 9 Gy) Stereotactic Radiosurgery for Large (>2 cm) Brain Metastases: A Comparative Analysis of Local Control and Risk of Radiation-Induced Brain Necrosis. Int J Radiat Oncol Biol Phys. 2016; 95(4): 1142–1148.
  29. Cagney DN, Alexander BM, Hodi FS, et al. Rapid progression of intracranial melanoma metastases controlled with combined BRAF/MEK inhibition after discontinuation of therapy: a clinical challenge. J Neurooncol. 2016; 129(3): 389–393.
  30. Park SS, Dong H, Liu X, et al. PD-1 restrains radiotherapy-induced abscopal effect. Cancer Immunol Res. 2015; 3(6): 610–619.
  31. Asna N, Livoff A, Batash R, et al. Radiation therapy and immunotherapy — a potential combination in cancer treatment. Curr Oncol. 2018; 25(5): e454–e460.
  32. Postow MA, Callahan MK, Barker CA, et al. Immunologic correlates of the abscopal effect in a patient with melanoma. N Engl J Med. 2012; 366(10): 925–931.
  33. Hiniker SM, Reddy SA, Maecker HT, et al. A Prospective Clinical Trial Combining Radiation Therapy With Systemic Immunotherapy in Metastatic Melanoma. Int J Radiat Oncol Biol Phys. 2016; 96(3): 578–588.
  34. Silk AW, Bassetti MF, West BT, et al. Ipilimumab and radiation therapy for melanoma brain metastases. Cancer Med. 2013; 2(6): 899–906.
  35. Twyman-Saint Victor C, Rech AJ, Maity A, et al. Radiation and dual checkpoint blockade activate non-redundant immune mechanisms in cancer. Nature. 2015; 520(7547): 373–377.
  36. Chandra RA, Wilhite TJ, Balboni TA, et al. A systematic evaluation of abscopal responses following radiotherapy in patients with metastatic melanoma treated with ipilimumab. Oncoimmunology. 2015; 4(11): e1046028.
  37. Local Tumor Treatment in Combination with Systemic Ipilimumab Immunotherapy Prolongs Overall Survival in Patients with Advanced Malignant Melanoma | Cancer Immunology Research [Internet]. [cited 2019 Sep 9]. Available from: https://cancerimmunolres.aacrjournals.org/content/early/2016/07/22/2326-6066.CIR-15-0156.
  38. Koller KM, Mackley HB, Liu J, et al. Improved survival and complete response rates in patients with advanced melanoma treated with concurrent ipilimumab and radiotherapy versus ipilimumab alone. Cancer Biol Ther. 2017; 18(1): 36–42.
  39. Liniker E, Menzies AM, Kong BY, et al. Activity and safety of radiotherapy with anti-PD-1 drug therapy in patients with metastatic melanoma. Oncoimmunology. 2016; 5(9): e1214788.
  40. Fang P, Jiang W, Allen P, et al. Radiation necrosis with stereotactic radiosurgery combined with CTLA-4 blockade and PD-1 inhibition for treatment of intracranial disease in metastatic melanoma. J Neurooncol. 2017; 133(3): 595–602.
  41. Crittenden M, Kohrt H, Levy R, et al. Current clinical trials testing combinations of immunotherapy and radiation. Semin Radiat Oncol. 2015; 25(1): 54–64.
  42. Ballo M, Ross M, Cormier J, et al. Combined-modality therapy for patients with regional nodal metastases from melanoma. Int J Radiat Oncol Biol Phys. 2006; 64(1): 106–113.
  43. Lauber K, Ernst A, Orth M, et al. Dying cell clearance and its impact on the outcome of tumor radiotherapy. Front Oncol. 2012; 2: 116.
  44. Meng X, Feng R, Yang L, et al. The role of radiation oncology in immuno-oncology. Oncologist. 2019; 24(Suppl 1): S42–S52.