A systematic review and meta‐analysis of locoregional treatments for in‐transit melanoma

In‐transit melanoma (ITM) metastases present a therapeutic challenge and management decisions can be difficult. There are multiple treatments available, with differing efficacy, and supported by different levels of evidence. The primary objective was to perform a systematic review and where suitable, a meta‐analysis of the literature reporting on the use of locoregional treatments for the management of ITM.

[1]  W. V. van Houdt,et al.  A systematic review and meta‐analysis of locoregional treatments for in‐transit melanoma , 2019, Journal of surgical oncology.

[2]  B. Dréno,et al.  Positive margins after surgical excision of locoregional cutaneous melanoma metastasis and their impact on patient outcome , 2018, European Journal of Dermatology.

[3]  A. Barbour,et al.  Intralesional PV‐10 for the treatment of in‐transit melanoma metastases—Results of a prospective, non‐randomized, single center study , 2018, Journal of surgical oncology.

[4]  H. Soyer,et al.  Diphenylcyclopropenone for the treatment of cutaneous in‐transit melanoma metastases – results of a prospective, non‐randomized, single‐centre study , 2017, Journal of the European Academy of Dermatology and Venereology : JEADV.

[5]  R. Gonzalez,et al.  Isolated Limb Infusion: A Single-Center Experience with Over 200 Infusions , 2017, Annals of Surgical Oncology.

[6]  B. Smithers,et al.  Results of a phase II, open‐label, non‐comparative study of intralesional PV‐10 followed by radiotherapy for the treatment of in‐transit or metastatic melanoma , 2017, Journal of surgical oncology.

[7]  F. Wright,et al.  Topical immunotherapy with diphencyprone (DPCP) for in-transit and unresectable cutaneous melanoma lesions: an inaugural Canadian series , 2017, Expert review of clinical immunology.

[8]  M. Henderson,et al.  Intralesional PV‐10 for in‐transit melanoma—A single‐center experience , 2016, Journal of surgical oncology.

[9]  A. Sarnaik,et al.  Intralesional rose bengal in melanoma elicits tumor immunity via activation of dendritic cells by the release of high mobility group box 1 , 2016, Oncotarget.

[10]  H. Soyer,et al.  A systematic review of non‐surgical treatments for lentigo maligna , 2016, Journal of the European Academy of Dermatology and Venereology : JEADV.

[11]  B. Coventry,et al.  Australian Multicenter Study of Isolated Limb Infusion for Melanoma , 2016, Annals of surgical oncology.

[12]  R. Olofsson Bagge,et al.  Health-Related Quality of Life for Patients Who have In-Transit Melanoma Metastases Treated with Isolated Limb Perfusion , 2016, Annals of Surgical Oncology.

[13]  B. King,et al.  100% Complete response rate in patients with cutaneous metastatic melanoma treated with intralesional interleukin (IL)-2, imiquimod, and topical retinoid combination therapy: results of a case series. , 2015, Journal of the American Academy of Dermatology.

[14]  J. Skitzki,et al.  The Role of Regional Therapies for in-Transit Melanoma in the Era of Improved Systemic Options , 2015, Cancers.

[15]  Troy Guthrie,et al.  Talimogene Laherparepvec Improves Durable Response Rate in Patients With Advanced Melanoma. , 2015, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[16]  A. Abernethy,et al.  Quality of Life After Isolated Limb Infusion for In-Transit Melanoma of the Extremity , 2015, Annals of Surgical Oncology.

[17]  R. Read,et al.  The Contemporary Role of Major Amputation in the Management of Advanced Limb Melanoma , 2015, Annals of Surgical Oncology.

[18]  K. Shannon,et al.  In-transit Melanoma Metastases: Incidence, Prognosis, and the Role of Lymphadenectomy , 2015, Annals of Surgical Oncology.

[19]  J. A. van der Hage,et al.  CO2 Laser Treatment for Regional Cutaneous Malignant Melanoma Metastases , 2015, Dermatologic surgery : official publication for American Society for Dermatologic Surgery [et al.].

[20]  M. Ross,et al.  Phase 2 Study of Intralesional PV-10 in Refractory Metastatic Melanoma , 2014, Annals of Surgical Oncology.

[21]  José H. Fregnani,et al.  Isolated limb infusion with hyperthermia and chemotherapy for advanced limb malignancy: factors influencing toxicity , 2014, ANZ journal of surgery.

[22]  C. Ariyan,et al.  Factors associated with response, survival, and limb salvage in patients undergoing isolated limb infusion , 2014, Journal of surgical oncology.

[23]  J. Thompson,et al.  Local and regional therapies for melanoma: Many arrows in the quiver , 2014, Journal of surgical oncology.

[24]  H. Hoekstra,et al.  Isolated limb perfusion for in‐transit melanoma metastases: Melphalan or TNF‐melphalan perfusion? , 2014, Journal of surgical oncology.

[25]  R. Saw,et al.  Topical immunotherapy with diphencyprone for in transit and cutaneously metastatic melanoma , 2014, Journal of surgical oncology.

[26]  D. Tyler,et al.  Resection of Residual Disease after Isolated Limb Infusion (ILI) Is Equivalent to a Complete Response after ILI-Alone in Advanced Extremity Melanoma , 2014, Annals of Surgical Oncology.

[27]  P. Lindnér,et al.  Long-term follow-up of 163 consecutive patients treated with isolated limb perfusion for in-transit metastases of malignant melanoma , 2013, International journal of hyperthermia : the official journal of European Society for Hyperthermic Oncology, North American Hyperthermia Group.

[28]  J. Wong,et al.  Isolated Limb Infusion in a Series of Over 100 Infusions: A Single-Center Experience , 2013, Annals of Surgical Oncology.

[29]  R. Turner,et al.  Combined Intralesional Bacille Calmette-Guérin (BCG) and Topical Imiquimod for In-transit Melanoma , 2012, Journal of immunotherapy.

[30]  L. Mortier,et al.  Topical treatment of cutaneous metastases of malignant melanoma using combined imiquimod and 5-fluorouracil , 2012, Investigational New Drugs.

[31]  D. Tyler,et al.  Patterns of Recurrence Following Complete Response to Regional Chemotherapy for In-Transit Melanoma , 2012, Annals of Surgical Oncology.

[32]  A. Quaba,et al.  Improving the quality of life in Melanoma – The role of the CO2 laser , 2012, Journal of cosmetic and laser therapy : official publication of the European Society for Laser Dermatology.

[33]  R. Gonzalez,et al.  The role of radical amputations for extremity tumors: A single institution experience and review of the literature , 2012, Journal of surgical oncology.

[34]  A. Mansfield,et al.  In-transit melanoma: an individualized approach. , 2011, Oncology.

[35]  C. Temple,et al.  Intra‐lesional interleukin‐2 for the treatment of in‐transit melanoma , 2011, Journal of surgical oncology.

[36]  A. Testori,et al.  Local and intralesional therapy of in‐transit melanoma metastases , 2011, Journal of surgical oncology.

[37]  A. Eggermont,et al.  20 Years Experience of TNF-Based Isolated Limb Perfusion for In-Transit Melanoma Metastases: TNF Dose Matters , 2011, Annals of Surgical Oncology.

[38]  C. Augustine,et al.  Current trends in regional therapy for melanoma: lessons learned from 225 regional chemotherapy treatments between 1995 and 2010 at a single institution. , 2011, Journal of the American College of Surgeons.

[39]  M. Trezzi,et al.  Vascular Complications following Isolated Limb Perfusion for Local Recurrence of Extremity Melanoma: A Case Report and Literature Review , 2011, International journal of vascular medicine.

[40]  M. Fung,et al.  Complete regression of subcutaneous and cutaneous metastatic melanoma with high-dose intralesional interleukin 2 in combination with topical imiquimod and retinoid cream , 2011, Melanoma research.

[41]  Merrick I Ross,et al.  Prospective multicenter phase II trial of systemic ADH-1 in combination with melphalan via isolated limb infusion in patients with advanced extremity melanoma. , 2011, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[42]  C. Garbe,et al.  High response rate after intratumoral treatment with interleukin‐2 , 2010, Cancer.

[43]  S. Mocellin,et al.  Long-Term Results of Melphalan-Based Isolated Limb Perfusion With or Without Low-Dose TNF for In-Transit Melanoma Metastases , 2010, Annals of Surgical Oncology.

[44]  D. Reintgen,et al.  Regional Therapy for Recurrent Metastatic Melanoma Confined to the Extremity: Hyperthermic Isolated Limb Perfusion vs. Isolated Limb Infusion , 2010, Cancers.

[45]  W. Hohenberger,et al.  Long-term outcome of hyperthermic isolated limb perfusion (HILP) in the treatment of locoregionally metastasised malignant melanoma of the extremities , 2010, International journal of hyperthermia : the official journal of European Society for Hyperthermic Oncology, North American Hyperthermia Group.

[46]  Jeffrey E Gershenwald,et al.  Final version of 2009 AJCC melanoma staging and classification. , 2009, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[47]  C. Augustine,et al.  Optimizing regional infusion treatment strategies for melanoma of the extremities , 2009, Expert review of anticancer therapy.

[48]  K. Shannon,et al.  Topical diphencyprone immunotherapy for cutaneous metastatic melanoma , 2009, The Australasian journal of dermatology.

[49]  D. Moher,et al.  Preferred reporting items for systematic reviews and meta-analyses: the PRISMA Statement , 2009, BMJ : British Medical Journal.

[50]  M. Ross,et al.  A multi-institutional experience of isolated limb infusion: defining response and toxicity in the US. , 2009, Journal of the American College of Surgeons.

[51]  N. Kandamany,et al.  Carbon dioxide laser ablation as first-line management of in-transit cutaneous malignant melanoma metastases , 2009, Lasers in Medical Science.

[52]  P. Kam,et al.  Major Amputation for Irresectable Extremity Melanoma After Failure of Isolated Limb Infusion , 2009, Annals of Surgical Oncology.

[53]  K. Brown,et al.  Isolated limb infusion with melphalan and dactinomycin for regional melanoma and soft-tissue sarcoma of the extremity: final report of a phase II clinical trial , 2009, Melanoma research.

[54]  I. Sperduti,et al.  Prognostic factors influencing tumor response, locoregional control and survival, in melanoma patients with multiple limb in-transit metastases treated with TNFalpha-based isolated limb perfusion. , 2009, In vivo.

[55]  P. Hersey,et al.  Chemoablation of metastatic melanoma using intralesional Rose Bengal , 2008, Melanoma research.

[56]  K. Delman,et al.  Therapy for unresectable recurrent and in-transit extremity melanoma. , 2008, Cancer control : journal of the Moffitt Cancer Center.

[57]  N. Aaronson,et al.  The health-related quality of life of long-term survivors of melanoma treated with isolated limb perfusion. , 2007, European journal of surgical oncology : the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology.

[58]  P. Kam,et al.  Long-term Results of Hyperthermic, Isolated Limb Perfusion for Melanoma: A Reflection of Tumor Biology , 2007, Annals of surgery.

[59]  A. Dalgleish,et al.  Phase I/II study of topical imiquimod and intralesional interleukin‐2 in the treatment of accessible metastases in malignant melanoma , 2007, The British journal of dermatology.

[60]  R. Nordquist,et al.  In situ photoimmunotherapy: a tumour‐directed treatment for melanoma , 2006, British Journal of Dermatology.

[61]  J. Thomas,et al.  Isolated Limb Perfusion With Melphalan and Tumor Necrosis Factor α for Advanced Melanoma and Soft-Tissue Sarcoma , 2006, Annals of Surgical Oncology.

[62]  Jeffrey E. Lee,et al.  Randomized multicenter trial of hyperthermic isolated limb perfusion with melphalan alone compared with melphalan plus tumor necrosis factor: American College of Surgeons Oncology Group Trial Z0020. , 2006, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[63]  K. Brown,et al.  A Phase II Trial of Isolated Limb Infusion With Melphalan and Dactinomycin for Regional Melanoma and Soft Tissue Sarcoma of the Extremity , 2006, Annals of Surgical Oncology.

[64]  W. Hohenberger,et al.  Hyperthermic isolated limb perfusion (HILP) in malignant melanoma. Experience with 101 patients. , 2006, European journal of surgical oncology : the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology.

[65]  D. Tyler,et al.  Predictors of outcome after hyperthermic isolated limb perfusion: role of tumor response. , 2005, Archives of surgery.

[66]  A. Eggermont,et al.  Major amputation for intractable extremity melanoma after failure of isolated limb perfusion. , 2005, European journal of surgical oncology : the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology.

[67]  A. Eggermont,et al.  One Hundred Consecutive Isolated Limb Perfusions With TNF-α and Melphalan in Melanoma Patients With Multiple In-Transit Metastases , 2004, Annals of surgery.

[68]  S. Gaffen,et al.  Overview of interleukin-2 function, production and clinical applications. , 2004, Cytokine.

[69]  A. Eggermont,et al.  Isolated limb perfusion for unresectable melanoma of the extremities. , 2004, Archives of surgery.

[70]  S. Gibson,et al.  Ten‐year experience of carbon dioxide laser ablation as treatment for cutaneous recurrence of malignant melanoma , 2004, The British journal of surgery.

[71]  Jeffrey E. Lee,et al.  Predictors and Natural History of In-Transit Melanoma After Sentinel Lymphadenectomy , 2004, Annals of Surgical Oncology.

[72]  H. Kerl,et al.  Locoregional Cutaneous Metastases of Malignant Melanoma and their Management , 2004, Dermatologic surgery : official publication for American Society for Dermatologic Surgery [et al.].

[73]  D. Sauder,et al.  Imiquimod: modes of action , 2003 .

[74]  C. Garbe,et al.  Phase II trial of intralesional therapy with interleukin-2 in soft-tissue melanoma metastases , 2003, British Journal of Cancer.

[75]  D. Altman,et al.  Measuring inconsistency in meta-analyses , 2003, BMJ : British Medical Journal.

[76]  D. Amadori,et al.  Restored T-cell activation mechanisms in human tumour-infiltrating lymphocytes from melanomas and colorectal carcinomas after exposure to interleukin-2 , 2003, British Journal of Cancer.

[77]  B. Bonnekoh,et al.  Imiquimod, a Topical Immune Response Modifier, in the Treatment of Cutaneous Metastases of Malignant Melanoma , 2002, Dermatology.

[78]  S. Thompson,et al.  Quantifying heterogeneity in a meta‐analysis , 2002, Statistics in medicine.

[79]  D. Tyler,et al.  Long-Term Survival in 2,505 Patients With Melanoma With Regional Lymph Node Metastasis , 2002, Annals of surgery.

[80]  M. Fabbri,et al.  Intralesional granulocyte‐monocyte colony‐stimulating factor followed by subcutaneous interleukin‐2 in metastatic melanoma: a pilot study in elderly patients , 2001, Journal of the European Academy of Dermatology and Venereology : JEADV.

[81]  A. Eggermont,et al.  Prophylactic isolated limb perfusion for localized, high-risk limb melanoma: results of a multicenter randomized phase III trial. European Organization for Research and Treatment of Cancer Malignant Melanoma Cooperative Group Protocol 18832, the World Health Organization Melanoma Program Trial 15, a , 1998, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[82]  P. Kam,et al.  Isolated limb infusion with cytotoxic agents: a simple alternative to isolated limb perfusion. , 1998, Seminars in surgical oncology.

[83]  Theresa,et al.  Expression and activity of signaling molecules in T lymphocytes obtained from patients with metastatic melanoma before and after interleukin 2 therapy. , 1996, Clinical cancer research : an official journal of the American Association for Cancer Research.

[84]  J. Thomas,et al.  Use of the carbon dioxide laser to manage cutaneous metastases from malignant melanoma , 1996, The British journal of surgery.

[85]  M. Lingam,et al.  Carbon dioxide laser ablation as an alternative treatment for cutaneous metastases from malignant melanoma , 1995, The British journal of surgery.

[86]  G. Mahrle,et al.  [Peritumoral administered IL-2-induced tumor regression in melanoma. Pilot study]. , 1994, Der Hautarzt; Zeitschrift fur Dermatologie, Venerologie, und verwandte Gebiete.

[87]  D. Faulds,et al.  Interleukin-2 , 2012, Drugs.

[88]  L. Ebskov Major amputation for malignant melanoma: An epidemiological study , 1993, Journal of surgical oncology.

[89]  R. M. Clement,et al.  Carbon dioxide laser ablation of cutaneous metastases from malignant melanoma , 1991, The British journal of surgery.

[90]  R. Smalley,et al.  Hyperthermic perfusion with chemotherapy for melanoma of the extremities , 1989, World Journal of Surgery.

[91]  S. Singletary,et al.  Patterns of relapse in 1001 consecutive patients with melanoma nodal metastases. , 1989, Archives of surgery.

[92]  C. Harland,et al.  REGRESSION OF CUTANEOUS METASTATIC MALIGNANT MELANOMA WITH TOPICAL DIPHENCYPRONE AND ORAL CIMETIDINE , 1989, The Lancet.

[93]  D. Coit,et al.  Major amputation for advanced malignant melanoma. , 1989, Surgery, gynecology & obstetrics.

[94]  N. Cascinelli,et al.  Regional non-nodal metastases of cutaneous melanoma. , 1986, European journal of surgical oncology : the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology.

[95]  W. McCarthy,et al.  Major amputations for melanoma. , 1983, The Australian and New Zealand journal of surgery.

[96]  J. Miller,et al.  The Inverse of the Freeman – Tukey Double Arcsine Transformation , 1978 .

[97]  M. Silverstein,et al.  BCG lmmunotherapy of Malignant Melanoma: Summary of a Seven-year Experience , 1974, Annals of surgery.

[98]  R. F. Ryan,et al.  Chemotherapy of Cancer: Regional Perfusion Utilizing an Extracorporeal Circuit , 1958, Annals of surgery.

[99]  J. Tukey,et al.  Transformations Related to the Angular and the Square Root , 1950 .

[100]  Matthew P. Goetz,et al.  NCCN CLINICAL PRACTICE GUIDELINES IN ONCOLOGY , 2019 .

[101]  A. Baccarelli,et al.  Pathologic Complete Response to Intralesional Interleukin-2 Therapy Associated with Improved Survival in Melanoma Patients with In-Transit Disease , 2014, Annals of Surgical Oncology.

[102]  B. Hesse,et al.  Tumour response after hyperthermic isolated limb perfusion for locally advanced melanoma. , 2014, Danish medical journal.

[103]  S. Steinberg,et al.  Analysis of factors influencing outcome in patients with in-transit malignant melanoma undergoing isolated limb perfusion using modern treatment parameters. , 2010, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[104]  L. Strobbe,et al.  Regional metastatic melanoma. Aspects of treatment and prognostic factors , 2001 .

[105]  R. Geronemus Argon laser for the treatment of cutaneous lesions. , 1995, Clinics in dermatology.