Safety profile and clinical outcome of adjuvant radiation therapy and intermediate-dose interferon in comparison with intermediate-dose interferon alone in patients with melanoma metastases in regional lymph nodes and unfavorable prognostic factors
DOI:
https://doi.org/10.32471/exp-oncology.2312-8852.vol-43-no-3.16524Keywords:
melanoma, radiation therapy, regional lymph node metastases, α2b-interferonAbstract
Summary. Aim: To assess the safety profile and efficacy of adjuvant radiation therapy and intermediate-dose interferon in comparison with intermediate-dose interferon alone in patients with synchronous and metachronous skin melanoma metastases in regional lymph nodes with unfavorable prognostic factors. Materials and Methods: 96 patients with synchronous and metachronous skin melanoma metastases in regional lymph nodes (stage III according to American Joint Committee on Cancer) and unfavorable prognostic factors were randomized in 2 groups: one of them (n = 45) received regional radiation therapy 50–55 Gy and intermediate dose of α2b-interferon (RT + IFN) in adjuvant setting and another one (n = 51) intermediate dose of α2b-interferon alone (IFN). Results: The most common adverse events in both groups were pyrexia and fatigue but grades 3–4 were observed more frequently in the RT + IFN group than in the IFN group (24.4 and 42.2% vs 11.8 and 27.5% respectively). 3-year recurrence-free survival was 78.5% in the RT + IFN group and 73.8% in the IFN group (p = 0.72), 3-year progression-free survival was 63.2% in the RT + IFN group comparing with 57.2% in the IFN group (p = 0.59) and 3-year overall survival was 77.1% and 66.7%, respectively (p = 0.29). Median of recurrence-free, progression-free and overall survival was not reached in any group. Conclusions: Radiation therapy and intermediate-dose interferon in adjuvant setting tends to improve recurrence-free, progression-free and overall survival comparing with intermediate-dose interferon alone in patients with synchronous and metachronous skin melanoma metastases in regional lymph nodes and unfavorable prognostic factors but it needs further investigation in larger groups of patients.
References
Korovin S, Fedorenko Z, Michailovich Y, et al. Burden of malignant melanoma in Ukraine in 2002–2013: incidence, mortality and survival. Exp Oncol 2020; 42: 324–9. https://doi.org/10.32471/exp-oncology.2312-8852.vol-42-no-4.15334.
Fedorenko Z, Michailovich Y, Goulak L, et al. Cancer in Ukraine 2019-2020. Bull Nat Cancer Registry of Ukraine 2021; 22: 38–9.
Emmett MS, Symonds KE, Rigby H, et al. Prediction of melanoma metastasis by the Shields index based on lymphatic vessel density. BMC Cancer 2010; 10: 1–8. https://doi.org/10.1186/1471-2407-10-208.
Ben-Ami E, Schachter J. Adjuvant treatment for stage III melanoma in the era of targeted medicine and immunotherapy. Melanoma Manag 2016; 3: 137–47. https://doi.org/10.2217/mmt-2016-0002.
Schuitevoerder D, Vining CC, Tseng J. Adjuvant therapy for cutaneous melanoma. Surg Oncol Clin 2020; 29: 455–65. https://doi.org/10.1016/j.soc.2020.02.009.
Michielin O, Van Akkooi A, Ascierto P, et al. Cutaneous melanoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol 2019; 30: 1884–901. https://doi.org/10.1093/annonc/mdz411.
Michielin O, van Akkooi A, Lorigan, P, et al. ESMO consensus conference recommendations on the management of locoregional melanoma: under the auspices of the ESMO Guidelines Committee. Ann Oncol 2020; 31: 1449–61. https://doi.org/10.1016/j.annonc.2020.07.005.
Garbe C, Amaral T, Peris K, et al. European consensus-based interdisciplinary guideline for melanoma. Part 2: treatment–update. Eur J Cancer 2019; 126: 159–77. https://doi.org/10.1016/j.ejca.2019.11.015.
Coit DG, Thompson JA, Albertini, et al. Cutaneous melanoma, version 2.2019, NCCN clinical practice guidelines in oncology. J Natl Compr Canc Netw 2019; 17: 367–402. https://doi.org/10.6004/jnccn.2019.0018.
Kandolf Sekulovic L, Guo J, Agarwala S, et al. Access to innovative medicines for metastatic melanoma worldwide: Melanoma World Society and European Association of Dermato-oncology survey in 34 countries. Eur J Cancer 2018; 104: 201–9. https://doi.org/10.1016/j.ejca.2018.09.013.
Agrawal S, Kane J, Guadagnolo B, et al. The benefits of adjuvant radiation therapy after therapeutic lymphadenectomy for clinically advanced, high-risk, lymph node-metastatic melanoma. Cancer 2009; 115: 5836–44. https://doi.org/10.1002/cncr.24627.
Gogas H, Kirkwood J, Sondak V. Chemotherapy for metastatic melanoma: time for a change? Cancer 2007; 109: 1–10. https://doi.org/10.1002/cncr.22427.
Korovin S, Kukushkina M. Adjuvant therapy of patients with metastases of skin melanoma in regional lymph nodes. Oncologiya 2007; 9: 377–9 (in Russian).
Dummer R, Hauschild A, Lindenblatt, N, et al. Cutaneous melanoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol 2015; 26: 126–32. https://doi.org/10.1093/annonc/mdv297.
Ives N, Succiu S, Eggermont A, et al. Adjuvant interferon-α for the treatment of high-risk melanoma: an individual patient data meta-analysis. Eur J Cancer 2017; 82: 171–83. https://doi.org/10.1016/j.ejca.2017.06.006.
Wang Y, Deng W, Li N, et al. Combining immunotherapy and radiotherapy for cancer treatment: current challenges and future directions. Front Pharmacol 2018; 9: 185. https://doi.org/10.3389/fphar.2018.00185.
Burnette BC, Liang H, Lee Y, et al. The efficacy of radiotherapy relies upon induction of type I interferon-dependent innate and adaptive immunity. Cancer Res 2011; 71: 2488–96. https://doi.org/10.1158/0008-5472.CAN-10-2820.
Ishikawa H, Ma Z, Barber GN. STING regulates intracellular DNAmediated, type I interferon-dependent innate immunity. Nature 2009; 461: 788–92. https://doi.org/10.1038/nature08476.
Deng L, Liang H, Xu M, et al. STING-dependent cytosolic DNA sensing promotes radiation-induced type I interferon-dependent antitumor immunity in immunogenic tumors. Immunity 2014; 41: 843–52. https://doi.org/10.1016/j.immuni.2014.10.019.
Vanpouille-Box C, Alard A, Aryankalayil MJ, et al. DNA exonuclease Trex1 regulates radiotherapy-induced tumour immunogenicity. Nat Commun 2017; 8: 15618. https://doi.org/10.1038/ncomms15618.
Downloads
Published
How to Cite
Issue
Section
License
Copyright (c) 2023 Experimental Oncology

This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
