Skip to main content

Advertisement

SpringerLink
Log in

In-transit metastatic cutaneous melanoma: current management and future directions

  • Review
  • Published:
Clinical & Experimental Metastasis Aims and scope Submit manuscript

Abstract

Management of in-transit melanoma encompasses a variety of possible treatment pathways and modalities. Depending on the location of disease, number of lesions, burden of disease and patient preference and characteristics, some treatments may be more beneficial than others. After full body radiographic staging is performed to rule out metastatic disease, curative therapy may be performed through surgical excision, intraarterial regional perfusion and infusion therapies, intralesional injections, systemic therapies or various combinations of any of these. While wide excision is limited in indication to superficial lesions that are few in number, the other listed therapies may be effective in treating unresectable disease. Where intraarterial perfusion based therapies have been shown to successfully treat extremity disease, injectable therapies can be used in lesions of the head and neck. Although systemic therapies for in-transit melanoma have limited specific data to support their primary use for in-transit disease, there are patients who may not be eligible for any of the other options, and current clinical trials are exploring the use of concurrent and sequential use of regional and systemic therapies with early results suggesting a synergistic benefit for oncologic response and outcomes.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

Data availability

Data sharing not applicable to this article as no datasets were generated or analyzed during the current study.

References

  1. Perone JA, Farrow N, Tyler DS, Beasley GM (2018) Contemporary approaches to in-transit melanoma. J Oncol Pract 14(5):292–300

    Article  PubMed  PubMed Central  Google Scholar 

  2. Wolf IH, Richtig E, Kopera D, Kerl H (2004) Locoregional cutaneous metastases of malignant melanoma and their management. Dermatol Surg 30(2 Pt 2):244–247

    PubMed  Google Scholar 

  3. Edge SB, Compton CC (2010). The American Joint Committee on Cancer: the 7th edition of the AJCC cancer staging manual and the future of TNM. Ann Surg Oncol 17(6):1471–1474.

  4. Gershenwald JE, Scolyer RA, Hess KR, et al. (2017) Melanoma staging: evidence-based changes in the american joint committee on cancer eighth edition cancer staging manual. CA Cancer J Clin 67(6):472–492.

  5. Pawlik TM, Ross MI, Thompson JF, Eggermont AMM, Gershenwald JE (2005) The risk of in-transit melanoma metastasis depends on tumor biology and not the surgical approach to regional lymph nodes. J Clin Oncol 23(21):4588–4590

    Article  PubMed  Google Scholar 

  6. Read RL, Haydu L, Saw RPM et al (2015) In-transit melanoma metastases: incidence, prognosis, and the role of lymphadenectomy. Ann Surg Oncol 22(2):475–481

    Article  PubMed  Google Scholar 

  7. Stucky C-CH, Gray RJ, Dueck AC et al (2010) Risk factors associated with local and in-transit recurrence of cutaneous melanoma. Am J Surg 200(6):770–775

    Article  PubMed  Google Scholar 

  8. Thomas JM, Clark MA (2004) Selective lymphadenectomy in sentinel node-positive patients may increase the risk of local/in-transit recurrence in malignant melanoma. Eur J Surg Oncol 30(6):686–691

    Article  CAS  PubMed  Google Scholar 

  9. Pawlik TM, Ross MI, Johnson MM et al (2005) Predictors and natural history of in-transit melanoma after sentinel lymphadenectomy. Ann Surg Oncol 12(8):587–596

    Article  PubMed  Google Scholar 

  10. Morton DL, Thompson JF, Cochran AJ et al (2014) Final trial report of sentinel-node biopsy versus nodal observation in melanoma. N Engl J Med 370(7):599–609

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Speicher PJ, Meriwether CH, Tyler DS (2015) Regional therapies for in-transit disease. Surg Oncol Clin N Am 24(2):309–322

    Article  PubMed  PubMed Central  Google Scholar 

  12. Testori A, Ribero S, Bataille V (2017) Diagnosis and treatment of in-transit melanoma metastases. Eur J Surg Oncol 43(3):544–560

    Article  CAS  PubMed  Google Scholar 

  13. Buzaid AC, Tinoco L, Ross MI, Legha SS, Benjamin RS (1995) Role of computed tomography in the staging of patients with local-regional metastases of melanoma. J Clin Oncol 13(8):2104–2108

    Article  CAS  PubMed  Google Scholar 

  14. Kuvshinoff BW, Kurtz C, Coit DG (1997) Computed tomography in evaluation of patients with stage III melanoma. Ann Surg Oncol 4(3):252–258

    Article  CAS  PubMed  Google Scholar 

  15. Johnson TM, Fader DJ, Chang AE et al (1997) Computed tomography in staging of patients with melanoma metastatic to the regional nodes. Ann Surg Oncol 4(5):396–402

    Article  CAS  PubMed  Google Scholar 

  16. Read RL, Thompson JF (2019) Managing in-transit melanoma metastases in the new era of effective systemic therapies for melanoma. Expert Rev Clin Pharmacol 12(12):1107–1119

    Article  CAS  PubMed  Google Scholar 

  17. Pointer DT Jr, Zager JS (2020) Management of Locoregionally Advanced Melanoma. Surg Clin North Am 100(1):109–125

    Article  PubMed  Google Scholar 

  18. Augustine CK, Jung SH, Sohn I et al (2010) Gene expression signatures as a guide to treatment strategies for in-transit metastatic melanoma. Mol Cancer Ther 9(4):779–790

    Article  CAS  PubMed  Google Scholar 

  19. Nan Tie E, Henderson MA, Gyorki DE (2019) Management of in-transit melanoma metastases: a review. ANZ J Surg 89(6):647–652

    Article  PubMed  Google Scholar 

  20. Coit DG, Andtbacka R, Bichakjian CK et al (2009) Melanoma. J Natl Compr Canc Netw 7(3):250–275

    Article  CAS  PubMed  Google Scholar 

  21. Squires MH 3rd, Delman KA (2013) Current treatment of locoregional recurrence of melanoma. Curr Oncol Rep 15(5):465–472

    Article  CAS  PubMed  Google Scholar 

  22. Dong XD, Tyler D, Johnson JL, DeMatos P, Seigler HF (2000) Analysis of prognosis and disease progression after local recurrence of melanoma. Cancer 88(5):1063–1071

    Article  CAS  PubMed  Google Scholar 

  23. Beasley GM, Hu Y, Youngwirth L et al (2017) Sentinel lymph node biopsy for recurrent melanoma: a multicenter study. Ann Surg Oncol 24(9):2728–2733

    Article  PubMed  Google Scholar 

  24. Creech O Jr, Krementz ET, Ryan RF, Winblad JN (1958) Chemotherapy of cancer: regional perfusion utilizing an extracorporeal circuit. Ann Surg 148(4):616–632

    Article  PubMed  PubMed Central  Google Scholar 

  25. Gabriel E, Skitzki J (2015) The role of regional therapies for in-transit melanoma in the era of improved systemic options. Cancers 7(3):1154–1177

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Noorda EM, Vrouenraets BC, Nieweg OE, van Geel BN, Eggermont AMM, Kroon BBR (2004) Isolated limb perfusion for unresectable melanoma of the extremities. Arch Surg 139(11):1237–1242

    Article  PubMed  Google Scholar 

  27. Moreno-Ramirez D, de la Cruz-Merino L, Ferrandiz L, Villegas-Portero R, Nieto-Garcia A (2010) Isolated limb perfusion for malignant melanoma: systematic review on effectiveness and safety. Oncologist 15(4):416–427

    Article  PubMed  PubMed Central  Google Scholar 

  28. Olofsson R, Mattsson J, Lindnér P (2013) Long-term follow-up of 163 consecutive patients treated with isolated limb perfusion for in-transit metastases of malignant melanoma. Int J Hyperthermia: Off J Eur Soc Hyperther Oncol, North Am Hyperther Group 29(6):551–557

    Article  CAS  Google Scholar 

  29. Grunhagen DJ, Verhoef C (2016) Isolated limb perfusion for stage III melanoma: does it still have a role in the present era of effective systemic therapy? Oncology (Williston Park) 30(12):1045–1052

    Google Scholar 

  30. Sanki A, Kam PCA, Thompson JF (2007) Long-term results of hyperthermic, isolated limb perfusion for melanoma: a reflection of tumor biology. Ann Surg 245(4):591–596

    Article  PubMed  PubMed Central  Google Scholar 

  31. Thompson JF, Kam PC, Waugh RC, Harman CR (1998) Isolated limb infusion with cytotoxic agents: a simple alternative to isolated limb perfusion. Semin Surg Oncol 14(3):238–247

    Article  CAS  PubMed  Google Scholar 

  32. Carr MJ, Sun J, Zager JS (2020) Isolated limb infusion: Institutional protocol and implementation. J Surg Oncol

  33. Kroon HM, Coventry BJ, Giles MH et al (2017) Safety and efficacy of isolated limb infusion chemotherapy for advanced locoregional melanoma in elderly patients: an australian multicenter study. Ann Surg Oncol 24(11):3245–3251

    Article  PubMed  Google Scholar 

  34. Teras J, Kroon HM, Miura JT, et al (2020) International multi-center experience of isolated limb infusion for in-transit melanoma metastases in octogenarian and nonagenarian patients. Ann Surg Oncol (in press)

  35. Teras J, Kroon HM, Zager JS (2020) ASO author reflection: isolated limb infusion for locally advanced melanoma in the extremely old patient is safe and effective. Ann Surg Oncol 27(5):1430–1431

    Article  PubMed  Google Scholar 

  36. O’Donoghue C, Perez MC, Mullinax JE et al (2017) Isolated limb infusion: a single-center experience with over 200 infusions. Ann Surg Oncol 24(13):3842–3849

    Article  PubMed  PubMed Central  Google Scholar 

  37. Miura JT, Kroon HM, Beasley GM et al (2019) Long-term oncologic outcomes after isolated limb infusion for locoregionally metastatic melanoma: an international multicenter analysis. Ann Surg Oncol 26(8):2486–2494

    Article  PubMed  PubMed Central  Google Scholar 

  38. Carr MJ, Sun J, Kroon HM, et al (2020) Oncologic outcomes after isolated limb infusion for advanced melanoma: an international comparison of the procedure and outcomes between the United States and Australia. Ann Surg Oncol

  39. Carr MJ, Kroon HM, Zager JS (2020) ASO Author reflections: return to isolated limb infusion for in-transit melanoma. Ann Surg Oncol

  40. Beasley GM, Petersen RP, Yoo J et al (2008) Isolated limb infusion for in-transit malignant melanoma of the extremity: a well-tolerated but less effective alternative to hyperthermic isolated limb perfusion. Ann Surg Oncol 15(8):2195–2205

    Article  PubMed  Google Scholar 

  41. Dossett LA, Ben-Shabat I, Olofsson Bagge R, Zager JS (2016) Clinical response and regional toxicity following isolated limb infusion compared with isolated limb perfusion for in-transit melanoma. Ann Surg Oncol 23(7):2330–2335

    Article  PubMed  Google Scholar 

  42. Raymond AK, Beasley GM, Broadwater G et al (2011) Current trends in regional therapy for melanoma: lessons learned from 225 regional chemotherapy treatments between 1995 and 2010 at a single institution. J Am Coll Surg 213(2):306–316

    Article  PubMed  PubMed Central  Google Scholar 

  43. Moller MG, Lewis JM, Dessureault S, Zager JS (2008) Toxicities associated with hyperthermic isolated limb perfusion and isolated limb infusion in the treatment of melanoma and sarcoma. Int J Hyperthermia 24(3):275–289

    Article  CAS  PubMed  Google Scholar 

  44. Wieberdink J, Benckhuysen C, Braat RP, van Slooten EA, Olthuis GA (1982) Dosimetry in isolation perfusion of the limbs by assessment of perfused tissue volume and grading of toxic tissue reactions. Eur J Cancer Clin Oncol 18(10):905–910

    Article  CAS  PubMed  Google Scholar 

  45. Hafstrom L, Rudenstam CM, Blomquist E et al (1991) Regional hyperthermic perfusion with melphalan after surgery for recurrent malignant melanoma of the extremities. Swedish Melanoma Study Group. J Clin Oncol 9(12):2091–2094

    Article  CAS  PubMed  Google Scholar 

  46. Santillan AA, Delman KA, Beasley GM et al (2009) Predictive factors of regional toxicity and serum creatine phosphokinase levels after isolated limb infusion for melanoma: a multi-institutional analysis. Ann Surg Oncol 16(9):2570–2578

    Article  PubMed  Google Scholar 

  47. Chai CY, Deneve JL, Beasley GM et al (2012) A multi-institutional experience of repeat regional chemotherapy for recurrent melanoma of extremities. Ann Surg Oncol 19(5):1637–1643

    Article  PubMed  Google Scholar 

  48. Belgrano V, Pettersson J, Nilsson JA, Mattsson J, Katsarelias D, Olofsson BR (2019) Response and Toxicity of Repeated Isolated Limb Perfusion (re-ILP) for Patients With In-Transit Metastases of Malignant Melanoma. Ann Surg Oncol 26(4):1055–1062

    Article  PubMed  PubMed Central  Google Scholar 

  49. Ariyan CE, Lefkowitz RA, Panageas K et al (2014) Safety and clinical activity of combining systemic ipilimumab with isolated limb infusion in patients with in-transit melanoma. J Clin Oncol 32(15):9078–9078

    Article  Google Scholar 

  50. Ariyan CE, Brady MS, Siegelbaum RH et al (2018) Robust Antitumor Responses Result from Local Chemotherapy and CTLA-4 Blockade. Cancer Immunol Res 6(2):189

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Coley WB (1991) The treatment of malignant tumors by repeated inoculations of erysipelas. With a report of ten original cases. 1893. Clin Orthop Relat Res. 262:3–11

    Article  Google Scholar 

  52. Miura JT, Zager JS (2018) Intralesional therapy as a treatment for locoregionally metastatic melanoma. Expert Rev Anticancer Ther 18(4):399–408

    Article  CAS  PubMed  Google Scholar 

  53. Testori A, Faries MB, Thompson JF et al (2011) Local and intralesional therapy of in-transit melanoma metastases. J Surg Oncol 104(4):391–396

    Article  PubMed  Google Scholar 

  54. Karakousis CP, Douglass HO Jr, Yeracaris PM, Holyoke ED (1976) BCG immunotherapy in patients with malignant melanoma. Arch Surg 111(6):716–718

    Article  CAS  PubMed  Google Scholar 

  55. Storm FK, Sparks FC, Morton DL (1979) Treatment for melanoma of the lower extremity with intralesional injection of bacille Calmette Guérin and hyperthermic perfusion. Surg Gynecol Obstetr 149(1):17–21

    CAS  Google Scholar 

  56. Tan JK, Ho VC (1993) Pooled analysis of the efficacy of bacille Calmette-Guerin (BCG) immunotherapy in malignant melanoma. J Dermatol Surg Oncol 19(11):985–990

    Article  CAS  PubMed  Google Scholar 

  57. Robinson JC (1977) Risks of BCG intralesional therapy: an experience with melanoma. J Surg Oncol 9(6):587–593

    Article  CAS  PubMed  Google Scholar 

  58. Cohen MH, Elin RJ, Cohen BJ (1991) Hypotension and disseminated intravascular coagulation following intralesional bacillus Calmette-Guérin therapy for locally metastatic melanoma. Cancer Immunol Immunother 32(5):315–324

    Article  CAS  PubMed  Google Scholar 

  59. Agarwala SS, Neuberg D, Park Y, Kirkwood JM (2004) Mature results of a phase III randomized trial of bacillus Calmette-Guerin (BCG) versus observation and BCG plus dacarbazine versus BCG in the adjuvant therapy of American Joint Committee on Cancer Stage I-III melanoma (E1673). Cancer 100(8):1692–1698

    Article  CAS  PubMed  Google Scholar 

  60. Liao W, Lin J-X, Leonard WJ (2013) Interleukin-2 at the crossroads of effector responses, tolerance, and immunotherapy. Immunity 38(1):13–25

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Temple-Oberle CF, Byers BA, Hurdle V, Fyfe A, McKinnon JG (2014) Intra-lesional interleukin-2 therapy for in transit melanoma. J Surg Oncol 109(4):327–331

    Article  CAS  PubMed  Google Scholar 

  62. Tarhini AA, Agarwala SS (2005) Interleukin-2 for the treatment of melanoma. Curr Opin Investig Drugs 6(12):1234–1239

    CAS  PubMed  Google Scholar 

  63. Eklund JW, Kuzel TM (2004) A review of recent findings involving interleukin-2-based cancer therapy. Curr Opin Oncol 16(6):542–546

    Article  CAS  PubMed  Google Scholar 

  64. Byers BA, Temple-Oberle CF, Hurdle V, McKinnon JG (2014) Treatment of in-transit melanoma with intra-lesional interleukin-2: a systematic review. J Surg Oncol 110(6):770–775

    Article  CAS  PubMed  Google Scholar 

  65. Hercus TR, Thomas D, Guthridge MA et al (2009) The granulocyte-macrophage colony-stimulating factor receptor: linking its structure to cell signaling and its role in disease. Blood 114(7):1289–1298

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Shi Y, Liu CH, Roberts AI et al (2006) Granulocyte-macrophage colony-stimulating factor (GM-CSF) and T-cell responses: what we do and don’t know. Cell Res 16(2):126–133

    Article  CAS  PubMed  Google Scholar 

  67. Hoeller C, Michielin O, Ascierto PA, Szabo Z, Blank CU (2016) Systematic review of the use of granulocyte-macrophage colony-stimulating factor in patients with advanced melanoma. Cancer Immunol Immunother: CII 65(9):1015–1034

    Article  CAS  PubMed  Google Scholar 

  68. Dranoff G, Jaffee E, Lazenby A et al (1993) Vaccination with irradiated tumor cells engineered to secrete murine granulocyte-macrophage colony-stimulating factor stimulates potent, specific, and long-lasting anti-tumor immunity. Proc Natl Acad Sci USA 90(8):3539–3543

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Si Z, Hersey P, Coates AS (1996) Clinical responses and lymphoid infiltrates in metastatic melanoma following treatment with intralesional GM-CSF. Melanoma Res 6(3):247–255

    Article  CAS  PubMed  Google Scholar 

  70. Nasi ML, Lieberman P, Busam KJ et al (1999) Intradermal injection of granulocyte-macrophage colony-stimulating factor (GM-CSF) in patients with metastatic melanoma recruits dendritic cells. Cytokines Cell Mol Ther 5(3):139–144

    CAS  PubMed  Google Scholar 

  71. Kubin RH, Grodsky GM, Carbone JV (1960) Investigation of Rose Bengal Conjugation. Proc Soc Exp Biol Med 104(4):650–653

    Article  CAS  PubMed  Google Scholar 

  72. Marsh RJ, Fraunfelder FT, McGill JI (1976) Herpetic corneal epithelial disease. Arch Ophthalmol 94(11):1899–1902

    Article  CAS  PubMed  Google Scholar 

  73. Mousavi H, Zhang X, Gillespie S, Wachter E, Hersey P (2006) Rose Bengal induces dual modes of cell death in melanoma cells and has clinical activity against melanoma. Melanoma Res 16

  74. Toomey P, Kodumudi K, Weber A et al (2013) Intralesional injection of rose bengal induces a systemic tumor-specific immune response in murine models of melanoma and breast cancer. PLoS ONE 8(7):e68561

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Thompson JF, Hersey P, Wachter E (2008) Chemoablation of metastatic melanoma using intralesional Rose Bengal. Melanoma Res 18(6):405–411

    Article  PubMed  Google Scholar 

  76. Thompson JF, Agarwala SS, Smithers BM et al (2015) Phase 2 Study of Intralesional PV-10 in Refractory Metastatic Melanoma. Ann Surg Oncol 22(7):2135–2142

    Article  PubMed  Google Scholar 

  77. Agarwala SS, Ross MI, Zager JS et al (2019) Phase 1b study of PV-10 and anti-PD-1 in advanced cutaneous melanoma. J Clin Oncol 37(15):9559–9559

    Article  Google Scholar 

  78. Agarwala SS, Ross M, Zager JS et al (2020) 1125P A phase Ib study of rose bengal disodium and anti-PD-1 in metastatic cutaneous melanoma: Results in patients naïve to immune checkpoint blockade. Ann Oncol 31:S756

    Article  Google Scholar 

  79. Zager JS, Sarnaik AS, Pilon-Thomas S et al (2020) 1123P A phase Ib study of rose bengal disodium and anti-PD-1 in metastatic cutaneous melanoma: Initial results in patients refractory to checkpoint blockade. Ann Oncol 31:S755–S756

    Article  Google Scholar 

  80. Kohlhapp FJ, Kaufman HL (2016) Molecular pathways: mechanism of action for talimogene laherparepvec, a new oncolytic virus immunotherapy. Clin Cancer Res 22(5):1048–1054

    Article  CAS  PubMed  Google Scholar 

  81. Conry RM, Westbrook B, McKee S, Norwood TG (2018) Talimogene laherparepvec: First in class oncolytic virotherapy. Hum Vaccin Immunother 14(4):839–846

    Article  PubMed  PubMed Central  Google Scholar 

  82. Johnson DB, Puzanov I, Kelley MC (2015) Talimogene laherparepvec (T-VEC) for the treatment of advanced melanoma. Immunotherapy 7(6):611–619

    Article  CAS  PubMed  Google Scholar 

  83. Liu BL, Robinson M, Han ZQ et al (2003) ICP345 deleted herpes simplex virus with enhanced oncolytic, immune stimulating, and anti-tumour properties. Gene Ther 10(4):292–303

    Article  CAS  PubMed  Google Scholar 

  84. Hu JC, Coffin RS, Davis CJ et al (2006) A phase I study of OncoVEXGM-CSF, a second-generation oncolytic herpes simplex virus expressing granulocyte macrophage colony-stimulating factor. Clin Cancer Res 12(22):6737–6747

    Article  CAS  PubMed  Google Scholar 

  85. Senzer NN, Kaufman HL, Amatruda T et al (2009) Phase II clinical trial of a granulocyte-macrophage colony-stimulating factor-encoding, second-generation oncolytic herpesvirus in patients with unresectable metastatic melanoma. J Clin Oncol 27(34):5763–5771

    Article  CAS  PubMed  Google Scholar 

  86. Andtbacka RH, Kaufman HL, Collichio F et al (2015) Talimogene laherparepvec improves durable response rate in patients with advanced melanoma. J Clin Oncol 33(25):2780–2788

    Article  CAS  PubMed  Google Scholar 

  87. Andtbacka RH, Ross M, Puzanov I et al (2016) Patterns of clinical response with talimogene laherparepvec (T-VEC) in patients with melanoma treated in the OPTiM Phase III clinical trial. Ann Surg Oncol 23(13):4169–4177

    Article  PubMed  PubMed Central  Google Scholar 

  88. Perez MC, Miura JT, Naqvi SMH et al (2018) Talimogene laherparepvec (TVEC) for the treatment of advanced melanoma: a single-institution experience. Ann Surg Oncol 25(13):3960–3965

    Article  PubMed  PubMed Central  Google Scholar 

  89. Louie RJ, Perez MC, Jajja MR et al (2019) Real-world outcomes of talimogene laherparepvec therapy: a multi-institutional experience. J Am Coll Surg 228(4):644–649

    Article  PubMed  Google Scholar 

  90. Puzanov I, Milhem MM, Minor D et al (2016) Talimogene laherparepvec in combination with ipilimumab in previously untreated, unresectable stage IIIB-IV melanoma. J Clin Oncol 34(22):2619–2626

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  91. Chesney J, Puzanov I, Collichio F et al (2018) Randomized, open-label phase II study evaluating the efficacy and safety of talimogene laherparepvec in combination with ipilimumab versus ipilimumab alone in patients with advanced, unresectable melanoma. J Clin Oncol 36(17):1658–1667

    Article  CAS  PubMed  Google Scholar 

  92. Ribas A, Dummer R, Puzanov I et al (2017) Oncolytic virotherapy promotes intratumoral t cell infiltration and improves Anti-PD-1 immunotherapy. Cell 170(6):1109-1119.e1110

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  93. Long GV, Dummer R, Ribas A et al (2015) A Phase I/III, multicenter, open-label trial of talimogene laherparepvec (T-VEC) in combination with pembrolizumab for the treatment of unresected, stage IIIb-IV melanoma (MASTERKEY-265). J Immunother Cancer 3(Suppl 2):P181–P181

    Article  PubMed Central  Google Scholar 

  94. Coit DG, Thompson JA, Algazi A et al (2016) NCCN guidelines insights: melanoma, Version 3.2016. J Natl Compr Canc Netw 14(8):945–958

    Article  PubMed  Google Scholar 

  95. Pardoll DM (2012) The blockade of immune checkpoints in cancer immunotherapy. Nat Rev Cancer 12(4):252–264

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  96. Weber J (2010) Immune checkpoint proteins: a new therapeutic paradigm for cancer–preclinical background: CTLA-4 and PD-1 blockade. Semin Oncol 37(5):430–439

    Article  CAS  PubMed  Google Scholar 

  97. McClure E, Carr MJ, Zager JS (2020) The MAP kinase signal transduction pathway: promising therapeutic targets used in the treatment of melanoma. Expert Rev Anticancer Ther 20(8):687–701

    Article  CAS  PubMed  Google Scholar 

  98. Long GV, Menzies AM, Nagrial AM et al (2011) Prognostic and clinicopathologic associations of oncogenic BRAF in metastatic melanoma. J Clin Oncol 29(10):1239–1246

    Article  PubMed  Google Scholar 

  99. Eggermont AMM, Chiarion-Sileni V, Grob J-J et al (2016) Prolonged Survival In Stage III melanoma with ipilimumab adjuvant therapy. N Engl J Med 375(19):1845–1855

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  100. Schachter J, Ribas A, Long GV et al (2017) Pembrolizumab versus ipilimumab for advanced melanoma: final overall survival results of a multicentre, randomised, open-label phase 3 study (KEYNOTE-006). Lancet 390(10105):1853–1862

    Article  CAS  PubMed  Google Scholar 

  101. Weber J, Mandala M, Del Vecchio M et al (2017) Adjuvant nivolumab versus ipilimumab in resected stage III or IV melanoma. N Engl J Med 377(19):1824–1835

    Article  CAS  PubMed  Google Scholar 

  102. Wolchok JD, Chiarion-Sileni V, Gonzalez R et al (2017) Overall survival with combined nivolumab and ipilimumab in advanced melanoma. N Engl J Med 377(14):1345–1356

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  103. Long GV, Hauschild A, Santinami M et al (2017) Adjuvant dabrafenib plus trametinib in stage III BRAF-mutated melanoma. N Engl J Med 377(19):1813–1823

    Article  CAS  PubMed  Google Scholar 

  104. Jiang BS, Beasley GM, Speicher PJ et al (2014) Immunotherapy following regional chemotherapy treatment of advanced extremity melanoma. Ann Surg Oncol 21(8):2525–2531

    Article  PubMed  PubMed Central  Google Scholar 

  105. Weber J, Glutsch V, Geissinger E et al (2020) Neoadjuvant immunotherapy with combined ipilimumab and nivolumab in patients with melanoma with primary or in transit disease. Br J Dermatol 183(3):559–563

    Article  CAS  PubMed  Google Scholar 

  106. Gibney GT, Messina JL, Fedorenko IV, Sondak VK, Smalley KSM (2013) Paradoxical oncogenesis–the long-term effects of BRAF inhibition in melanoma. Nat Rev Clin Oncol 10(7):390–399

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  107. Sharma P, Hu-Lieskovan S, Wargo JA, Ribas A (2017) Primary, adaptive, and acquired resistance to cancer immunotherapy. Cell 168(4):707–723

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  108. Kroon HM, Moncrieff M, Kam PCA, Thompson JF (2008) Outcomes following isolated limb infusion for melanoma. A 14-Year experience. Ann Surg Oncol 15(11):3003

    Article  PubMed  Google Scholar 

Download references

Funding

This paper was not funded.

Author information

Author notes

  1. James Sun

    Present address: Department of Surgery, University Hospitals, Cleveland Medical Center, Cleveland, OH, USA

Authors and Affiliations

  1. Department of Oncologic Sciences, University of South Florida Morsani College of Medicine, 12901 Bruce B Downs Blvd, Tampa, FL, 33612, USA

    Ayushi Patel & Jonathan S. Zager

  2. Department of Cutaneous Oncology, Moffitt Cancer Center, 10920 North McKinley Drive, Tampa, FL, 33612, USA

    Michael J. Carr, James Sun & Jonathan S. Zager

Authors
  1. Ayushi Patel
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Michael J. Carr
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. James Sun
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Jonathan S. Zager
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Jonathan S. Zager.

Ethics declarations

Conflict of interest

A.P and M.J.C have no conflicts of interest to disclose. J.S. has received research funding from Amgen. J.S.Z has advisory board relationships with Novartis, Sanofi/Regeneron, Merck; receives research funding from Amgen, Delcath Systems, Philogen, Provectus; consults for Castle Biosciences and Philogen, speaker’s bureau for Castle Biosciences, Pfizer and SunPharma. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Presented at the 8th International Cancer Metastasis Congress in San Francisco, CA, USA from October 25–27, 2019 (http://www.cancermetastasis.org). To be published in an upcoming Special Issue of Clinical and Experimental Metastasis: Novel Frontiers in Cancer Metastasis.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Patel, A., Carr, M.J., Sun, J. et al. In-transit metastatic cutaneous melanoma: current management and future directions. Clin Exp Metastasis 39, 201–211 (2022). https://doi.org/10.1007/s10585-021-10100-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10585-021-10100-3

Keywords

Search

Navigation